Wildlife and Marine Animals:Marine Mammals as Sentinel Species for Oceans and Human Health.

Wildlife and Marine Animals
Marine Mammals as Sentinel Species for
Oceans and Human Health
G. D. Bossart1
Abstract
The long-term consequences of climate change and potential environmental degradation are likely to include aspects of disease
emergence in marine plants and animals. In turn, these emerging diseases may have epizootic potential, zoonotic implications, and
a complex pathogenesis involving other cofactors such as anthropogenic contaminant burden, genetics, and immunologic dysfunction.
The concept of marine sentinel organisms provides one approach to evaluating aquatic ecosystem health. Such sentinels are
barometers for current or potential negative impacts on individual- and population-level animal health. In turn, using marine sentinels
permits better characterization and management of impacts that ultimately affect animal and human health associated with
the oceans. Marine mammals are prime sentinel species because many species have long life spans, are long-term coastal residents,
feed at a high trophic level, and have unique fat stores that can serve as depots for anthropogenic toxins. Marine mammals may be
exposed to environmental stressors such as chemical pollutants, harmful algal biotoxins, and emerging or resurging pathogens.
Since many marine mammal species share the coastal environment with humans and consume the same food, they also may serve
as effective sentinels for public health problems. Finally, marine mammals are charismatic megafauna that typically stimulate an
exaggerated human behavioral response and are thus more likely to be observed.
Keywords
marine mammals, sentinel species, ecosystem health, human health
As the effects of climate change and potential environmental
degradation are debated and better characterized, worldwide
concern is being raised about the health of the earth’s aquatic
ecosystems.40,148,206,212 The long-term consequences of environmental
change on aquatic ecosystems are not well characterized
but are likely to include aspects of disease emergence
in aquatic plants and animals.206 In turn, these emerging diseases
may have epizootic potential, zoonotic implications, and
a complex pathogenesis involving other cofactors such as
anthropogenic contaminant burden, genetics, and immunologic
dysfunction.30,181 Emerging diseases have themselves become
new drivers of environmental change since they can cause
extinction of endangered species; alter the ratios of predators,
prey, competitors, and recyclers necessary for healthy, wellfunctioning
ecosystems; and alter habitat already threatened
by the emergence of discontinuities (ie, habitat fragmentation)
and climate change.62
Ocean health is inextricably linked to human health on a
global scale as well. Connections between the health of
humans, animals, and the environments in which they live are
well recognized and recently have been referred to as ‘‘one
health, one medicine.’’ The ‘‘one health, one medicine’’ worldwide
strategy for expanding interdisciplinary collaborations
and communications in all aspects of health begins to address
these critical relationships.
The concept of marine sentinel organisms provides one
approach to evaluating aquatic ecosystem health. Such sentinels
are used to gain early warnings about current or potential
negative impacts on individual- and population-level animal
health.29 In turn, such warnings permit better characterization
and management of these impacts that ultimately affect human
and animal health associated with the oceans. Marine mammals
are described as prime sentinels because many species have
long life spans, are long-term coastal residents, feed at a
high trophic level, and have large blubber stores that can
serve as depots for anthropogenic chemicals and toxins.
7,15,29,30,110,111,154,155,184,234 Finally, marine mammals are
charismatic megafauna that typically stimulate an exaggerated
human behavioral response and are thus more likely to be
observed.21 Therefore, health concerns that affect these species
1 Georgia Aquarium, Atlanta, Georgia, and Division of Comparative Pathology,
Department of Pathology, School of Medicine, University of Miami, Miami,
Florida
Corresponding Author:
Gregory D. Bossart, VMD, PhD, Georgia Aquarium, 225 Baker St. N.W.,
Atlanta, GA 30313
Email: gbossart@georgiaaquarium.org
Veterinary Pathology
48(3) 676-690
ª The American College of
Veterinary Pathologists 2011
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0300985810388525
http://vet.sagepub.com
may make humans more likely to pay attention to ocean health
issues.
Emerging Infectious and Neoplastic
Disease in Marine Mammals
Emerging and reemerging viral, bacterial, protozoal, and
fungal diseases have been described in marine mammals.
Additionally, complex diseases involving emerging infectious
and neoplastic components have been reported, and these diseases
may provide important information on aquatic ecosystem
and public health.
Morbillivirus Infection
Morbillivirus infections are responsible for recent widespread
epizootics and mortality in cetaceans.129,130,131,177,225,226
A cetaceanmorbillivirus caused a massive epizootic that resulted
in the death of an estimated 2,500 dolphins or approximately 50%
of the inshore population of Atlantic bottlenose dolphins
(Tursiops truncatus) in 1987–1988.129 This large-scale epizootic
was followed by further die-offs of bottlenose dolphins in theGulf
ofMexico in 1993 and 1994.Morbillivirus antigen and characteristic
lesions were detected in tissues from both epizootics, and
morbillivirus RNA was demonstrated by reverse transcription
polymerase chain reaction (PCR) testing.129,130,120,204
A second major morbillivirus epizootic killed several
thousand striped dolphins (Stenella coeruleoalba) along the
Spanish Mediterranean coast from 1990 to 1992, and more
recently an epizootic occurred in 2007.57-59,177 Historically,
2 strains of cetacean morbillivirus have been reported to infect
odontocete cetacean populations worldwide: dolphin morbillivirus
(DMV) and porpoise morbillivirus (PMV).57,58,223 DMV
and PMV appear to be closely related strains of a cetacean morbillivirus
and are distinct from phocine distemper virus and
canine distemper virus and more closely related to the ruminant
morbilliviruses and measles virus.14,10,232 Additionally, a novel
morbillivirus was identified in a long-finned pilot whale (Globicephala
melas) that died off the coast of New Jersey and may
represent a third member of the cetacean morbillivirus
group.217 A central role for infection in pilot whales (Globicephala
sp.) has been suggested on the basis of high seroprevalence
in samples obtained during multiple stranding events
for both G. melas and G. macrorhynchus dating back to
1982.61 The high rates of seroprevalence and gregarious nature
of the species led to the hypothesis that pilot whales may serve
as reservoirs for cetacean morbilliviruses and transmit the
agent to other cetaceans; however, the nature of enzootic infection
in Globicephala, if it occurs, remains unresolved.61
In general, DMV infection is not considered an endemic
infection, and it is speculated that a decline in herd immunity
and an increase in population density will render dolphin populations
susceptible to new epizootics.33 However, evidence for
chronic infection consisting of nonsuppurative encephalitis
characterized by DMV antigen in the brain in the absence of
other systemic involvement has been reported in striped
dolphins.59 Similarly, DMV titers and antigen persistence in
the brain, in the absence of typical morbillivirus lesions or systemic
involvement, have both been observed in Indo-Pacific
bottlenose dolphins (Tursiops aduncus), further illustrating the
complexity of this infection (G. D. Bossart, unpublished data).
Furthermore, in an ongoing comprehensive Atlantic bottlenose
dolphin health assessment program in the Indian River Lagoon
(IRL), Florida, positive fluctuating morbillivirus titers and seroconversion
were recently reported in this dolphin population
that has strong site fidelity.33 Seropositivity was detected in
IRL dolphins less than 6 years of age as well as in dolphins
that were alive during the 1987–1988 epizootic. During the
study period, pathologic and immunohistochemical findings
from stranded IRL dolphins did not demonstrate typical
morbillivirus-associated lesions or the presence of morbillivirus
antigen. The findings suggest that recurring endemic morbillivirus
transmission and subclinical infections are occurring
in the absence of widespread mortality in IRL dolphins.
In cases of widespread cetacean morbilliviral disease, disease
surveillance becomes an important component of population
health and epidemiology and may provide information on population
susceptibility to epizootics that can significantly impact
ecosystem health and stability.
Brucellosis
Brucellosis is a zoonotic disease of terrestrial and marine mammals.
Brucella spp. were first isolated in 1994 from tissues collected
at necropsy from stranded harbor seals (Phoca vitulina),
harbor porpoise (Phocoena phocoena), and common dolphins
(Delphinus delphis) from Scotland and from an aborted fetus
of a bottlenose dolphin in the United States.63,194,195 The isolation
of Brucella has since been described from a wide variety of
marine mammals including Atlantic white-sided dolphin
(Lagenorhynchus acutus), striped dolphin, hooded seal (Cystophora
cristata), gray seal (Halichoerus grypus), Pacific harbor
seal (Phoca vitulina richardsi), minke whale, and white
beaked dolphin (Lagenorhynchus albirostris).42,75,76,78,105,176
Furthermore, strong serological evidence exists to suggest
that marine mammal Brucella infections are globally widespread
among marine mammal species and have a high
prevalence.46,107,161-163,169,191,195,214,221,224 Marine mammal
Brucella strains are distinct from the terrestrial Brucella species,
and recently 2 new species, B. pinnipedialis and B. ceti,
were described.77 New molecular data confirm that there are
significant subtypes within the newly described marine mammal
Brucella species, which add to a body of evidence that
could lead to the recognition of additional species or subspecies
within this group.47,136
Compared with the reported high global seroprevalence of
marinemammal Brucella spp. infection, clinical disease does not
appear to be common. In one study,minke whales (Balaenoptera
acutorostrata) and Bryde’s whales (Balaenoptera edeni) in the
western North Pacific were reported to have chronic purulent or
granulomatous orchitis associated with positive Brucella antibody
titers.169 Two cases of Brucella placentitis and abortion
Bossart 677
have been reported in captive Atlantic bottlenose dolphins.149
Neurobrucellosis recently was reported in striped dolphins and
was characterized by lymphoplasmacytic and histiocytic nonsuppurative
meningoencephalitis.84,95 Dolphins with neurobrucellosis
typically are PCR, serologically, and immunohistochemically
positive to Brucella spp and Brucella ceti and may be isolated
from cerebrospinal fluid. In dolphins, B. ceti has tropism for placental
and fetal tissues. Vertical transmission and the possibility
of horizontal transmission to newborns have been postulated.95
Thus, bacteriamay be shed as in Brucella-infected domestic livestock.
Moreover, the localization of the bacteria in particular
organs suggests the possibility of transmission through sexual
intercourse and may ensure the prevalence of both clinical and
latent infections.95 It appears that striped dolphins constitute a
highly susceptible host and a potential reservoir for B. ceti transmission.
84,95,158 Marine mammal Brucella strains are capable of
infecting humans and livestock and thus represent an important
zoonotic consideration despite the observation that human clinical
disease does not appear to be common.174,207,235 Notably, in
one review, none of the 3 human patients infected with marine
mammal brucellosis had direct contact with marine mammals,
although all had consumed raw seafood.235 These findings suggest
that more extensive studies of the presence and distribution
ofmarinemammal Brucella genotypes are needed before the zoonotic
significance can be evaluated. Additionally, global surveillance
is required to fully understand the distribution, ecology, and
genetic relatedness of Brucella isolates from marine mammals
that become valuable sentinels for evaluating the aquatic health
impacts of this infectious agent.
Leptospirosis
Leptospirosis is a zoonotic disease infecting a broad range of
mammalian hosts and is reemerging globally.12 California sea
lions (Zalophus californianus) have experienced recurrent outbreaks
of leptospirosis since 1970, and the infection is thought
to be enzootic.1,142,228 Leptospirosis, primarily caused by L.
interrogans serovar Pomona, is known to cause abortions and
renal disease in California sea lions with clinicopathologic features
similar to domestic animals.56,87 Histologically, a lymphoplasmacytic
interstitial nephritis with tubular necrosis is
present with the spirochete identified in the renal tubular
epithelium and free in the lumina. In newborns and aborted
fetuses, the disease is characterized by subcutaneous hemorrhage
and hyphema.142,228
Recent research to elucidate the epidemiology of leptospirosis
in California sea lions demonstrated that the disease is
enzootic but also occurs in outbreaks of acute disease every
4–5 years.133 The latter findings call into question the apparent
contradiction between maintenance hosts of leptospirosis,
which experience chronic but largely asymptomatic infections,
and accidental hosts, which suffer acute illness or death as a
result of disease spillover from reservoir species. Furthermore,
environmental risk factors for sea lion leptospirosis may
include exposure to dogs and dog parks or factors associated
with them.167 The sea lion/leptospirosis system raises questions
regarding the accepted view of the epidemiology of this important
zoonosis, especially since leptospirosis has resurged in
humans and domestic dogs in California.4,144
Protozoal Infection
Protozoal infection is a major cause of mortality among southern
sea otters (Enhydra lutris nereis). Infections with protozoal
pathogens Toxoplasma gondii and Sarcocystis neurona were
the cause of death in approximately 25% of the freshly dead sea
otters examined from 1998 to 2001.121,122 Introduced and invasive
terrestrial mammals including domestic cats and opossums
are the respective definitive hosts for these protozoa. Oocysts
from cat feces wash into seawater, where they can survive for
at least 24 months and serve as a source of infection via transport
hosts.128 A seroprevalence analysis showed T. gondii
infection in 52% of beached sea otters and 38% in live sea
otters sampled along the California coast, with a clear association
between proximity of freshwater inputs into the ocean and
infection.147 Southern sea otters consume a wide variety of
benthic marine invertebrates; their daily food consumption is
equivalent to 25–35% of their body weight.111 In the laboratory,
filter feeding sea otter prey species such as blue mussels
(Mytilis spp.) accumulate T. gondii oocysts that remain infective
for weeks.8 As nearshore predators, otters serve as sentinels
of protozoal pathogen flow into the marine environment
since they share the same environment and consume some of
the same foods as humans such as mussels, clams, and
crabs.111,146 Eating improperly prepared seafood containing
oocysts may result in human toxoplasmosis, which is a potentially
fatal infection in immunocompromised patients and a
well-documented cause of serious fetal malformations.37,60
Investigation into the processes promoting protozoal infections
in sea otters provides a better understanding of terrestrial parasite
flow and the emergence of disease at the interface between
wildlife, domestic animals, and humans.44,68,146
Mycotic Disease
The emergence of lobomycosis was recently reported in dolphins
along Florida’s Atlantic coast and in North Carolina.26,29,189,198
Lobomycosis is a rare chronic mycotic disease of the skin and
subcutaneous tissues caused by a yeast-like organism known as
Lacazia loboi.17Dolphins and humans are the only species known
to be naturally susceptible to infection with Lacazia loboi. The
clinicopathologic manifestations of lobomycosis in humans and
dolphins are similar and consist of focal to locally extensive
verrucoid to nodular lesions that typically progress slowly over
the course of years without involvement of internal organs. The
tissue response consists of multifocal dermal granulomas. Within
granulomas, Lacazia can be demonstrated as yeast-like organisms,
6–12 mm in diameter with thick, refractile walls, arranged
singly or in chains connected by tube-like bridges.17,189 The
organism has not been cultured to date in vitro; therefore, diagnosis
depends on identification of the characteristic yeast-like
cells in tissue or exudates.
678 Veterinary Pathology 48(3)
The IRL is an endemic area for the lobomycosis in dolphins
with a prevalence of 10–12%.189 Recent research indicates that
the disease is associated with humoral and cell-mediated
immunosuppression.17,188 The spatial distribution of lobomycosis
within the IRL suggests that environmental factors contribute
to the expression of the disease.159 Mercury levels in
dolphin tissues in the IRL are high and may play a role in the
disruption of immune function, increasing susceptibility to
opportunistic infections.188,208,209 Limited evidence exists to
suggest that lobomycosis may be transferred from infected animals
to people.189 However, the high prevalence of lobomycosis
in the dolphin population of a Florida coastal region, which
is used extensively for recreational purposes, raises concerns
for zoonotic or common source transmission. Thus, from several
perspectives, lobomycosis in bottlenose dolphins represents
an animal sentinel of environmental and ecosystem
change, with particular implications for human health in populations
inhabiting coastal environments.
Viral Disease
Diseases with complex multifactorial etiologies associated with
novel viral infections are being characterized in marine mammals.
For example, approximately 20% of sexually mature
stranded California sea lions have urogenital cancer, which
often metastasizes and is associated with a novel gammaherpesvirus,
designated otarine herpesvirus-1 (OtHV-1).38,39,118,132
Other cofactors potentially involved in the pathogenesis of urogenital
carcinoma in sea lions include exposure to anthropogenic
contaminants that persist in the sea lions’ feeding
grounds and genetic factors, specifically inbred sea lions and
those with a specific MHC genotype.2,35,238
Recently, sexually transmitted orogenital papillomatosis that
occasionally undergoes transformation to metastatic squamous
cell carcinoma was found to be frequently associated with a
novel herpesvirus and newly sequenced papillomaviruses
(TtPV-1, TtPV-2) in Atlantic bottlenose dolphins.28,32,183,185-187
The dolphin disease is associated with immunologic perturbations
and, in some instances, with high levels of anthropogenic
contaminants, including mercury and infection with immunosuppressive
cetacean morbilliviruses.32,33,208,209 Cutaneous
papillomatosis associated with another novel papillomavirus
(TmPV-1) was documented in Florida manatees (Trichechus
manatus latirostris) with virally productive papillomas associated
with immunosuppression.23,182 In manatees, it is thought
that cutaneous papillomas are caused by activation of latent
infection and reinoculation from active infection with concurrent
immunologic suppression as a cofactor in disease pathogenesis.
23 Because related papillomaviruses are associated
with human disease, including cervical cancer, dolphins and
manatees may be good models for understanding oncogenesis
mechanisms in humans. These combined data suggest that
interactions occur among genes, anthropogenic toxins, immunologic
factors, and/or oncogenic viruses in these common
marine mammals that share a coastal environment with
humans.2,29,188,238
Antibiotic Resistant Bacteria
Other confirmed or suspected infectious disease agents have
been reported in marine mammals that may have ecosystem
or human health implications.19,94,135,165,166,230,226 One significant
concern to public health authorities is the emergence of
antibiotic-resistant species of bacteria among animals and
humans. Widespread evidence of antibiotic-resistant bacteria
was recently described in northern elephant seals (Mirounga
angustirostris) and bottlenose dolphins, the latter as part of
health assessment studies from the coastal waters of Charleston
(CHS), South Carolina, and the IRL.85,201,202,211 Direct release
of resistant bacterial species and/or unused antimicrobial
agents into the aquatic environment appears to affect these dolphin
populations. Twenty-five percent of Escherichia coli fecal
isolates from IRL and CHS dolphins demonstrated resistance to
1 or more antibiotics. Disturbingly, a small number of
methicillin-resistant also were reported from dolphins. The
results suggest that the transfer of resistance from humans or
domestic animals may occur or that antibiotics are reaching the
marine environment, creating selective genetic adaptation.
85,201,202 Thus, from an aquatic perspective, dolphins
appear to be prime sentinels for this important public health
problem.
Anthropogenic Chemicals
Marine mammals are exposed to a variety of persistent organohalogen
compounds (POCs) and inorganic pollutants that
bioaccumulate in marine ecosystems, resulting in high tissue
contaminant concentrations. In particular, marine mammals
from coastal regions associated with dense human populations
and greater industrial and agricultural activities have high tissue
concentrations of POCs.6,64,101,171-173 In addition to being
apex predators, small cetaceans have several anatomic and
life-history features that contribute to the accumulation of lipophilic
pollutants, which may increase susceptibility to other
anthropogenic stressors.64 Cetacean species have extensive fat
stores that accumulate high levels of POCs. During periods of
fasting, starvation, lactation, or other physiological demands,
these contaminants may be mobilized, which may redistribute
traditional contaminants as well as emerging chemicals of concern.
The redistribution of these contaminants may affect adult
and perinatal health. Furthermore, the lower capacity for degradation
of these chemicals in these species exacerbates toxic
effects.16,215
High levels of contaminants documented in marine mammals
include legacy chemicals such as the organochlorine pesticides
including dichlorodiphenylethanes (ie, DDTs), dieldrin,
chlordanes, hexachlorocyclohexanes (HCHs), polychlorinated
dioxins, dibenzofurans, and polychlorinated biphenyls
(PCBs)64,86,93,115,116,151,153,164 and emerging compounds such
as polybrominated diphenyl ethers (PBDEs),64,65,103,112,116,143,222
perfluorinated chemicals (PFCs),34,64,117 hexabromocyclododecanes,
and polybrominated dimethoxybiphenyls.113,231,240
Hydroxylated PCBs and PBDEs were reported in various tissues
Bossart 679
of belugawhales, bottlenose dolphins, and killerwhales (Orcinus
orca).11,102,143
In particular, the widespread coastal distribution of bottlenose
dolphins and their role as apex predators support their
relevance as important sentinel species for biomonitoring spatial
and temporal trends in contaminants.29,64,66,67,184,210,234
Interestingly, in a novel POC risk assessment model, marine
mammals also have been used as sentinel species for Arctic
ecosystem and public health.97-100,123,134,236 The accumulation
of POCs in Native populations from Arctic subsistence communities
has raised questions concerning the suitability of terrestrial
and marine wildlife from this region for human
consumption.100,168,199,200 For Arctic residents dependent upon
marine resources, a clear human connection exists with marine
mammal health since Arctic marine mammal species consume
similar prey and many marine mammal species are themselves
consumed by indigenous peoples.
Persistent organohalogen compounds are resistant to environmental
degradation and persist for long periods, becoming
widely distributed geographically and accumulating in the fatty
tissue of humans and wildlife. The associations of adverse
health effects with POCs in marine mammals have been
arguably linked to increased infectious disease susceptibility,
5,91,108,109,196,197 immunosuppression,43,51,54,55,156,157,196
reproductive impairment,3,43,190,109 endocrine disruption,
73,74,106,175,213,216 and neoplasia.43,138,140,160,238 In toxicology
testing in laboratory species, convincing evidence exists
for the toxicopathologic effects of many of these contaminants
on endocrine, neurologic, reproductive, developmental, immunologic,
and cellular systems.13,41,45,53,67,79,104,125,126,170,193,229
Beluga whales (Delphinapterus leucas) from the St. Lawrence
estuary are one of the most extensively and consistently
studied groups of free-ranging marine mammals in relation
to POCs and other contaminants and the development of neoplasia.
50,92,137,140,141,160 Beluga whales from the St. Lawrence region
develop a wide variety of neoplasms, many of which are of similar
types to those seen in domestic species and in
humans.48,49,139,140,160 Exposure to carcinogenic contaminants
such as POCs in the food chain is a speculated cause of the high
prevalence of neoplasia in this population of whales.50,92,137,140
Heavy metal levels have often been measured from the
blood of marine mammals, but the significance of the levels
found is not fully understood. High levels of mercury have been
reported in dolphins from the Gulf and Atlantic coasts of
Florida and Australia.127,208,209,237 For example, the IRL
dolphin population has the highest mean concentrations of
mercury in blood and skin from the limited set of studies of
free-ranging bottlenose dolphins reported to date. The concentrations
of mercury found in IRL dolphins exceeded the EPA
benchmark of mercury in cord blood for humans.208,209 Correlations
between mercury and selenium have been reported in
many marine mammal species, and the ability of marine mammals
to withstand large concentrations of mercury is believed
to be partly due to this protective pairing with selenium.127,237
Further studies are required to explore the effects of mercury on
these marine mammal populations as well as the potential
implications for humans that inhabit the same coastal
ecosystems.
The interactions of mercury and selenium may play a role in
the cardiomyopathy (CMP) reported in pygmy sperm whales
(Kogia breviceps) and dwarf sperm whales (Kogia sima). The
disease in Kogia spp. has been described primarily in stranded
adult male whales from the southeastern Atlantic Ocean, but it
also occurs in Pacific Ocean whales.18,31 More than half of
documented adult Kogia spp. strandings exhibit signs of
chronic progressive idiopathic CMP or some state of myocardial
degeneration. The cause of this complex disorder remains
unknown. However, factors speculated to contribute to
the development of CMP in these species include genetics,
infectious agents, contaminants, biotoxins, and dietary intake
(vitamins, selenium, mercury, and prooxidants).31 In a recent
age-controlled study of K. breviceps, both mercury and selenium
concentrations increased with animal age and progression
of CMP (C. E. Bryan, personal communication). Whales with
CMP had greater overall protein oxidation, and selenium protein
patterns were different between animals with no myocardial
lesions and those with CMP, suggesting that selenium
protein expression is altered with the disease state in pygmy
sperm whales. The latter studies increased knowledge of CMP
in pygmy and dwarf sperm whales and may also provide complementary
information benefiting other affected species.
Using marine mammals as sentinels may provide important
clues about the cumulative and synergistic effects of the mixture
of the aforementioned contaminants, which is an emerging
issue that requires attention.150,153,172 Marine mammals are
exposed to a wide admixture of legacy POCs and PCBs, emerging
contaminants such as PBDEs and PFCs, their metabolites
and/or degradation products, heavy metals, and natural marine
biotoxins associated with harmful algal blooms (see below).
The significance of these multiple co-exposures is still unclear,
but the potential exists for additive and/or synergistic effects on
the immunologic, neurologic, endocrine, and reproductive systems
of not only marine mammals but also humans who inhabit
the same coastal ecosystems.
Harmful Algal Blooms
Harmful algal blooms (HABs), and the potent neurotoxins they
produce, have been associated with mass mortalities of dolphins,
sea lions, southern sea otters, Florida manatees, Mediterranean
monk seals (Monachus monachus), gray whales
(Eschrichtius robustus), and humpback whales (Megaptera
novaeangliae).22,24,71,72,80,88,111,220 The range of biotoxins produced
by HABs is extensive, and these toxins directly or indirectly
affect human health. Biotoxins associated with HABs
include brevetoxins, the cause of neurotoxic shellfish poisoning;
saxitoxins, the cause of paralytic shellfish poisoning; okadaic
acid, the cause of diarrheic shellfish poisoning; domoic
acid, the cause of amnesic shellfish poisoning; and others.
124,227 The HAB problem is significant, is growing worldwide,
and poses a major threat to human and ecosystem
health.81,119 The global pandemic of HABs has been
680 Veterinary Pathology 48(3)
interpreted as a reflection of ecosystem instability and a threat
to public health.62 Thus, marine mammals appear to be good
sentinels for the ecosystem and public health effects of
HABs.20,29
Domoic Acid
Domoic acid (DA) is a neurotoxin produced by diatoms of the
genus Pseudo-nitzschia, which targets the limbic system. This
toxin causes excitotoxicity and damage to neuronal pathways
responsible for the learning and recall of sequences underlying
spatial memory as well as restraining seizure-prone circuitry
associated with temporal lobe epilepsy.89,179 A unique hallmark
ofDA intoxication in humans is loss of short-term memory, thus
the term amnesic shellfish poisoning. Recurrent outbreaks of
DA poisoning along the California coast have caused stranding
of several thousand sea lions, and DA is now viewed as a major
cause of reproductive failure.36,52,83,89,203 The primary peracute
microscopic lesions of DA toxicity in adult sea lions are
microvesicular hydropic degeneration within the neuropil of the
hippocampus, amygdala, pyriform lobe, and other limbic structures.
Acutely, ischemic neuronal necrosis develops and is particularly
apparent in the granular cells of the dentate gyrus and
the pyramidal cells within the hippocampus cornu ammonis
(CA) sectors CA4, CA3, and CA1. Chronically, gliosis, mild
nonsuppurative inflammation, and loss of laminar organization
in affected areas are found.205 Myocardial necrosis and edema
have also been reported.88 Histopathologic findings associated
with abortion and premature birth include systemic and localized
inflammation and bacterial infections of amniotic origin,
placental abruption, and brain edema.83 A degenerative cardiomyopathy
associated with exposure to DA, which is beyond central
neurologic disease, represents another recently reported
syndrome in California sea lions and may contribute to morbidity
and mortality.239 Furthermore, it has been suggested that DA
intoxication may be potentiated by organochlorine burden.219
Recent observations have defined a chronic disease in juvenile
California sea lions characterized by epilepsy and unusual
behaviors.82 This emerging chronic juvenile sea lion disease
has been proposed to result from in utero toxicity to DA.180
Research suggests that sublethal DA doses may progress to
chronic epileptic disease similar to temporal lobe epilepsy in
humans178 and that magnetic imaging the hippocampus of sea
lions exposed to DA may be a useful antemortem diagnostic
technique.152 Acute high-dose DA intoxication may lead to
sudden death but those animals that survive the initial bout of
seizures may develop neurological disease with behavioral
changes and increased severity of spontaneous seizures in the
absence of the DA diatom blooms. Thus, sea lions may provide
important information on how marine mammals and other species,
including humans, respond to DA intoxication including
the possible association with epilepsy. Additionally, since sea
lion strandings in California appear to be a very sensitive indicator
of DA in the marine environment, it has recently been
suggested that their monitoring be included in public health
surveillance plans.52
Domoic acid also may affect southern sea otters, gray
whales (Eschrichtius robustus), and pygmy and dwarf sperm
whales. In 2003, an unusual mortality event was declared in
southern sea otters by the US Fish and Wildlife Service and
NOAA/National Marine Fisheries Service. Blooms of
Pseudo-nitzschia australis were associated with this event.111
In 2000, an abnormally high number of gray whales were
stranded in California, and these strandings were associated
with Pseudo-nitzchia australis blooms and high tissue levels
as of DA.227 Finally, DA was recently detected in urine and
fecal samples recovered from pygmy sperm whales and dwarf
sperm whales stranding along the US Atlantic coast from 1997
to 2008.69 Although blooms of Pseudo-nitzschia are associated
with repeated large-scale marine mammal mortalities on the
west coast of the United States, there is no documented history
of similar blooms on the southeast US coast, and there were no
observed Pseudo-nitzschia blooms in the region associated
with any of the Kogia spp. strandings. Since myocardial damage
is a feature of DA toxicity in sea lions and DA intoxication
has been identified as a risk factor for myocarditis and dilated
CMP in southern sea otters, an association may exist between
this toxin and the Kogia cardiomyopathy described
above.89,122,239 Toxin accumulation in these pelagic whale species
may be an indication of harmful algal bloom activity in
offshore areas not currently being monitored and thus reflect
shifts in ecosystem health that deserve further investigation.
Brevetoxins
Recent, and often unprecedented, endangered Florida manatee
and Atlantic bottlenose dolphin epizootics have been associated
with potent marine neurotoxins known as brevetoxins,
which are produced by the ‘‘red tide’’ dinoflagellate Karenia
brevis.20,24,70 Brevetoxins are known to kill large numbers of
fish and cause illness in humans who ingest toxic filterfeeding
shellfish (neurotoxic shellfish poisoning) or inhale
toxic aerosols. The pathogenesis of brevetoxicosis is suspected
to involve direct inhalation of toxins (in manatees) or ingestion
of toxins in food sources (in manatees and dolphins).20,25,27
At least 149 manatees died in an unprecedented epizootic along
the southwest coast of Florida, and a detailed pathologic investigation
was conducted.20 At about the same time, a bloom of
K. brevis was present in the same area. Brevetoxins were isolated
in quantities from 2- to 15- fold above control levels in
stomach contents, liver, kidney, and lung from dead manatees
using a synaptosomal binding assay. Grossly, severe nasopharyngeal,
pulmonary, hepatic, renal, and cerebral congestion was
present in all cases. Nasopharyngeal and pulmonary edema and
hemorrhage were also seen. Consistent microscopic lesions
consisted of severe catarrhal rhinitis, pulmonary hemorrhage
and edema, multiorgan hemosiderosis, and nonsuppurative leptomeningitis.
Immunohistochemical staining using a polyclonal
primary antibody to brevetoxin (GAB) showed intense
positive staining of lymphocytes and macrophages in the lung,
liver, and secondary lymphoid tissues. Lymphocytes and
macrophages associated with the inflammatory lesions of the
Bossart 681
nasal mucosa and meninges were also positive for brevetoxin.
These findings implicated brevetoxicosis as a component of
and the likely primary cause of the epizootic.20 It was postulated
that the route of brevetoxin exposure was inhalation of
aerosolized toxins causing the upper respiratory inflammation
and dissemination of toxin via macrophages and lymphocytes,
ultimately resulting in acute agonal cardiovascular collapse.
A chronic hemolytic process was also postulated resulting in
the widespread hemosiderosis since similar changes have been
reported in birds and fish exposed to brevetoxins. Additionally,
retrospective histopathologic and immunohistochemical studies
demonstrated that other manatee epizootics were likely due
to the incidental ingestion of filter-feeding ascidians that contained
brevetoxins.
Manatees from Florida’s coastlines have frequent potential
brevetoxin exposure because red tide blooms are common in
these areas. Important new data indicate that brevetoxin vectors
such as seagrasses can result in delayed or remote manatee
exposure, causing intoxication in the absence of toxinproducing
dinoflagelates.71 Thus, unexpected toxin vectors
may account for manatee deaths long after or remote from a
dinoflagellate bloom. Therefore, manatee mortality resulting
from brevetoxicosis may not necessarily be acute but may
occur after chronic inhalation and/or ingestion.20,24 Immunohistochemical
studies of manatee tissues with interleukin-1b–
converting enzyme showed positive staining with a cellular
tropism similar to GAB.20,24 The data suggested that brevetoxicosis
might initiate the release of inflammatory mediators that
culminate in fatal toxic shock. Additionally, prolonged nonlethal
toxin exposure may compromise normal immunologic
responses, predisposing manatees exposed to brevetoxins to
opportunistic disease.233 Interestingly, the inhalational route
of brevetoxin exposure in manatees is shared with humans,
making manatees an important sentinel species for this emerging
health problem. Increases in human pulmonary emergency
room visits are temporally related to red tide and can
have significant human health and economic impact.9,96,119
Over the past 20 years, investigations into marine mammal
mortality events have provided insight into the ecosystem
events, vectors, clinical signs, and pathologic effects of HAB
biotoxin exposure. Compelling evidence supports the involvement
of saxitoxins, DA, and brevetoxins in marine mammal
morbidity and mortality.20,72,80,89 However, confirmation that
these toxins are sole etiologic agents for disease remains problematic
because the peracute, acute, and chronic biotoxin
effects in marine mammals are unknown. Additionally, it is
likely these toxins are involved in multifactorial disease involving
infectious agents, immunologic perturbations, and other
pathologic processes that makes interpretation challenging.
Conclusion
In the past 20 years, dedicated marine mammal research has
resulted in an increase in reporting of marine mammal disease.
90 At the same time, the appearance of true emerging and
reemerging diseases in marine mammals is also suggested
historically and by the scientific literature. This phenomenon
may be related to complex factors such as climate change, toxins,
and immunosuppression, with coastal marine mammals
particularly at risk since many inhabit an environment more
affected by human activity.29,226 Potential increased environmental
pressure on marine mammals may provoke more frequent
epizootics, help disseminate possible zoonotic
pathogens, and increase the prevalence and severity of infectious
illnesses worldwide. Marine mammals are useful sentinels
for emerging and reemerging infectious and neoplastic
disease, the effects of anthropogenic toxins, and the impacts
of the global pandemic of harmful algal blooms. Many of these
diseases have direct public health implications, whereas others
may be indicative of an environmental distress syndrome. To
this end, marine mammals are proving to be good sentinels for
ocean and human health given their many unique natural attributes.
Marine mammal research will undoubtedly expand as
new species are evaluated and better tools to assess health are
developed. This approach provides a new avenue for better
understanding the interface between evolving ecosystem and
public health issues.29 Ultimately, it is in our own best interest
to investigate all wildlife health patterns that could potentially
affect our own well-being since three-fourths of all emerging
infectious diseases of humans are zoonotic, most originate in
wildlife, and their incidence is increasing.114,145,192,218
Acknowledgements
Tissues from free-ranging dolphins were collected under National
Marine Fisheries Service Scientific Research Permit No. 998-1678
issued to Dr. Bossart as part of the Health and Risk Assessment of Bottlenose
Dolphin Project (HERA) conducted in the Indian River
Lagoon, Florida, and the coastal waters of Charleston, South Carolina.
The author thanks the entire dedicated dolphin HERA project staff,
with special thanks extended to Dr. Pat Fair, Dr. Juli Goldstein,
Dr. John Reif, Dr. Forrest Townsend, Larry Hansen, and the members
of the NMFS Marine Mammal Stranding program. Special thanks to
Bruce Gordon, Dr. Pat Fair, and Dr. R. H. DeFran for editorial assistance
and Dr. Mike Hyatt for data collection assistance. Finally, the
author gratefully acknowledges Stephen D. McCulloch for his tireless
energy and contributions to marine mammal research.
Declaration of Conflicting Interests
The authors declared that they had no conflicts of interest with respect
to their authorship or the publication of this article.
Financial Disclosure/Funding
Harbor Branch Oceanographic Institute at Florida Atlantic University
‘‘Protect Florida Dolphin’’ program and NOAA Fisheries Marine
Mammal Health and Stranding Response Program partially supported
this work.
References
1. Acevedo-Whitehouse K, de la Cueva H, Gulland FMD, et al: Evidence
of Leptospira interrogans infection in California sea lion
pups from the Gulf of California. J Wildl Dis 39:145–151, 2003.
2. Acevedo-Whitehouse K, Gulland FMD, Greig D, et al: Disease
susceptibility in California sea lions. Nature 422:35, 2003.
682 Veterinary Pathology 48(3)
3. Addison RF: Organochlorines and marine mammal reproduction.
Can J Fish Aquat Sci 46:360–368, 1989.
4. Adin CA, Cowgill LD: Treatment and outcome of dogs with leptospirosis:
36 cases (1990–1998). J Am Vet Med Assoc 216:371–
375, 2000.
5. Aguilar A, Borrell A: Abnormally high polychlorinated biphenyl
levels in striped dolphins (Stenella coeruleoalba) affected by the
1990–1992 Mediterranean epizootic. Sci Total Environ 154:237–
347, 1994.
6. Aguilar A, Borrell A, Reijnders PJH: Geographical and temporal
variation in levels of organochlorine contaminants in marine
mammals. Mar Environ Res 53:425–452, 2002.
7. Aguirre AA, Tabor AA: Introduction: marine mammals as sentinels
of marine ecosystem health. EcoHealth 1:236–238, 2004.
8. Arkush KD, Miller MA, Leutenegger CM, et al: Molecular and
bioassay-based detection of Toxoplasma gondii oocyst uptake
by mussels (Mytilius galloprovincialis). Int J Parasitol 33:1087–
1097, 2003.
9. Backer LC, Fleming LE, Rowan A, et al: Recreational exposure to
aerosolized brevetoxins during Florida red tide events. Harmful
Algae 2:19–28, 2003.
10. Barrett T, Visser IKG, Mamaev LV, et al: Dolphin and porpoise
morbilliviruses are genetically distinct from phocine distemper
virus. Virology 193:1010–1012, 1993.
11. Bennett ER, Ross PS, Alaee M, et al: Chlorinated and brominated
organic contaminants and metabolites in the plasma and diet of a
captive killer whale (Orcinus orca). Mar Pollut Bull 58(7):1078–
1083, 2009.
12. Bharti AR, Nally JE, Ricaldi JN, et al: Leptospirosis: a zoonotic
disease of global importance. Lancet Infect Dis 3:757–771, 2003.
13. Birnbaum LS, Staskal DF: Brominated flame retardants: cause for
concern? Environ Health Perspect 112:9–117, 2004.
14. Blixenkrone-Moller M, Bolt G, Gottschalck E, et al: Comparative
analysis of the gene encoding the nucleocapsid protein of dolphin
morbillivirus reveals its distant evolutionary relationship to
measles virus and ruminant morbilliviruses. J Gen Virol
75:2829–2834, 1994.
15. Bonde R, Aguirre AA, Powell J: Manatees as sentinels of marine
ecosystem health: are they the 2000 pound canaries? Ecohealth
1:255–262, 2004.
16. Boon JP, Oostingh I, Van der Meeer J, et al: A model for the
bioaccumulation of chlorobiphenyl congeners in marine mammals.
Environ Toxicol Pharmacol 270:237–251, 1994.
17. Bossart GD: A suspected acquired immunodeficiency in an Atlantic
bottlenosed dolphin with lobomycosis and chronic-active
hepatitis. J Am Vet Med Assoc 185:1413–1414, 1984.
18. Bossart GD, Odell DK, Altman NH: Cardiomyopathy in stranded
pygmy and dwarf sperm whales. J Am Vet Med Assoc 187:1137–
1140, 1985.
19. Bossart GD, Ewing R, Herron AJ, et al: Immunoblastic malignant
lymphoma in dolphins: ultrastructural and immunohistochemical
features. J Vet Diagn Invest 9:454–458, 1997.
20. Bossart GD, Baden DG, Ewing R, et al: Brevetoxicosis in manatees
(Trichechus manatus latirostris) from the 1996 epizootic:
gross, histologic and immunohistochemical features. Toxicol
Pathol 26:276–282, 1998.
21. Bossart GD: The Florida manatee: on the verge of extinction?
J Am Vet Med Assoc 214:10–15, 1999.
22. Bossart GD. Manatees. In: Marine Mammal Medicine, ed.
Dierauf L and Gulland F, pp. 939–960. CRC Press, Boca Raton,
FL, 2001.
23. Bossart GD, Ewing R, Lowe M, et al: Viral papillomatosis in
Florida manatees (Trichechus manatus latirostris). Exp Mol
Pathol 72:37–48, 2002.
24. Bossart GD, Baden DG, Ewing RY, et al: Manatees and
brevetoxicosis. In: Molecular and Cell Biology of Marine
Mammals, ed. Pfeiffer C, pp. 205–212. Krieger, Melbourne, FL,
2002.
25. Bossart GD, Meisner R, Rommel SA, et al: Pathological features
of the Florida manatee cold stress syndrome. Aquatic Mammals
29(1):9–17, 2003.
26. Bossart GD, Meisner R, Varela R, et al: Pathologic findings in
stranded Atlantic bottlenose dolphins (Tursiops truncatus) from the
Indian River Lagoon, Florida. Florida Scientist 66(3):226–238,
2003.
27. Bossart GD, Meisner R, Rommel SA, et al: Pathologic findings in
Florida manatees (Trichechus manatus latirostris). Aquatic Mammals
30(3):434–440, 2004.
28. Bossart GD, Ghim S, Rehtanz M, et al: Orogenital neoplasia in
Atlantic bottlenose dolphins (Tursiops truncatus). Aquatic Mammals
31(4):473–480, 2005.
29. Bossart GD: Marine mammals as sentinel species for oceans and
human health. Oceanography 19(2):44–47, 2006.
30. Bossart GD: Emerging diseases in marine mammals: from dolphins
to manatees. Microbe 11(2):544–549, 2007.
31. Bossart GD, Hensley G, Goldstein J, et al: Cardiomyopathy and
myocardial degeneration in stranded pygmy (Kogia breviceps)
and dwarf sperm (Kogia sima) whales. Aquatic Mammals
33(2):214–222, 2007.
32. Bossart GD, Romano TA, Peden-Adams, et al: Hematological,
biochemical and immunological findings in Atlantic bottlenose
dolphins (Tursiops truncatus) with orogenital papillomas. Aquatic
Mammals 34(2):166–177, 2008.
33. Bossart GD, Reif JS, Schaefer AM, et al: Morbillivirus infection
in free-ranging Atlantic bottlenose dolphins (Tursiops
truncatus) from the southeastern United States: seroepidemiologic
and pathologic evidence of subclinical infection. Vet
Microbiol 143:160–166, 2010.
34. Bossi R, Riget FF, Dietz R, et al: Preliminary screening of perfluorooctane
sulfonate (PFOS) and other fluorochemicals in fish,
birds and marine mammals from Greenland and the Faroe Islands.
Environ Pollut 136(2):323–329, 2005.
35. Bowen L, Aldridge BM, Delong R, et al: An immunogenetic basis
for the high prevalence of urogenital cancer in a free-ranging population
of California sea lions (Zalophus californianus). Immunogenetics
56(11):846–848, 2005.
36. Brodie EC, Gulland FMD, Greig DJ, et al: Domoic acid causes
reproductive failure in California sea lions (Zalophus californianus).
Mar Mammal Sci 22(3):700–707, 2006.
37. Brown AS, Schaefer CA, Quesenberry CP Jr, et al: Maternal
exposure to toxoplasmosis and risk of schizophrenia in adult offspring.
Am J Psychiatry 162:767–773, 2005.
Bossart 683
38. Buckles EL, Lowenstine LJ, DeLong RL, et al: age-prevalence of
otarine herpesvirus-1, a tumor-associated virus, and possibility of
its sexual transmission in California sea lions. Vet Microbiol
120(1–2):1–8, 2007.
39. Buckles EL, Lowenstine LJ, Funke C, et al: Otarine herpesvirus-
1, not papillomavirus, is associated with endemic tumours in California
sea lions (Zalophus californianus). J Comp Pathol
135(4):183–189, 2006.
40. Cao L, Caldeira K: Atmospheric CO2 stabilization and ocean
acidification. Geophys Res Lett 35:L19609, 2008.
41. Capdevielle M, Van Egmond R, Whelan, M, et al: Consideration
of exposure and species sensitivity of triclosan in the freshwater
environment. Integr Environ Assess Manag 4:15–23, 2008.
42. Clavareau C, Wellemans V, Walravens K, et al: Phenotypic and
molecular characterization of a Brucella strain isolated from a
minke whale (Balaenoptera acutorostrata). Microbiology
144:3267–3273, 1998.
43. Colborn T, Smolen MJ: Cetaceans and contaminants. In: Toxicology
of Marine Mammals, ed. Vos JG, Bossart GD, Fournier M,
and O’Shea T, pp. 291–232. Taylor & Francis, London, 2003.
44. Conrad P, Kreuder C, Mazet J, et al: Linkages between cats,
run-off and brain disease in sea otters. Paper presented at the
Symposium, Marine Mammals on the Frontline: Indicators for
Ocean and Human Health. American Association for the
Advancement of Science, Annual Meeting, St. Louis, MO, February
18, 2006.
45. Crofton KM, Paul KB, DeVito MJ, et al: Short-term in vivo exposure
to the water contaminant triclosan: evidence for disruption of
thyroxine. Environ Toxicol Pharmacol 24:194–197, 2007.
46. Dawson CE: Anti-Brucella antibodies in pinnipeds of Australia.
Microbiology Aust 26:87–89, 2005.
47. Dawson CE, Stubberfield EJ, Perrett LL, et al: Phenotypic and
molecular characterization of Brucella isolates from marine mammals.
BMC Microbiol 8:224, 2008.
48. De Guise S, Lagace A, Beland P: Gastric papillomas in eight St.
Lawrence beluga whales (Delphinapterus leucas). J Vet Diagn
Invest 6:385–388, 1994.
49. De Guise S, Lagace A, Beland P: Tumors in St. Lawrence beluga
whales (Delphinapterus leucas). Vet Pathol 31:444–449, 1994.
50. De Guise S: Possible mechanisms of action of environmental contaminants
on St. Lawrence beluga whales. Envir Health Perspect
103:73–77, 1995.
51. De Guise S, Martineau D, Beland P, et al: Effects of in vitro
exposure of beluga whale leukocytes to selected organochlorines.
J Toxicol Environ Health A 55:479–493, 1998.
52. de la Riva GT, Johnson CK, Gulland FM, et al: Association of an
unusual marine mammal mortality event with Pseudo-nitzschia
spp. blooms along the southern California coastline. J Wildl Dis
45(1):109–121, 2009.
53. DeLorenzo ME, Keller JM, Arthur CD, et al: Toxicity of the antimicrobial
compound triclosan and formation of the metabolite
methyl-triclosan in estuarine systems. Environ Toxicol 23:224–
232, 2008.
54. de Swart RL, Ross PS, Vedder EJ, et al: Impairment of immunological
function in harbour seals (Phoca vitulina) feeding on fish
from polluted coastal waters. Ambio 23:155–159, 1994.
55. de Swart RL, Ross PS, Vos JG, et al: Impaired immunity in
harbour seals (Phoca vitulina) exposed to bioaccumulation
environmental contaminants: review of a long term feeding study.
Environ Health Perspect 104:823–828, 1996.
56. Dierauf LA, Vandenbroek DJ, Roletto J, et al: An epizootic of
leptospirosis in California sea lions. J Am Vet Med Assoc
187:1145–1148, 1985.
57. Domingo ML, Ferrer L, Pumarola M, et al: Morbillivirus in
dolphins. Nature 348:21, 1990.
58. Domingo M, Visa J, Pumarola M, et al: Pathologic and immunocytochemical
studies of morbillivirus infection in striped dolphins
(Stenella coeruleoalba). Vet Pathol 29:1–10, 1992.
59. Domingo M, Vilafranca M, Visa J, et al: Evidence for chronic
morbillivirus infection in the Mediterranean striped dolphin (Stenella
coeruleoalba). Vet Microbiol 44:229–239, 1995.
60. Dubey JP, Beattie CP: Toxoplasmosis of Animals and Man. CRC
Press, Boca Raton, FL, 1998.
61. Duignan PJ, House C, Geraci JR, et al: Morbillivirus infection in
two species of pilot whales (Globicephala sp.) from the western
Atlantic. Mar Mammal Sci 11:150–162, 1995.
62. Epstein PR, Chivian E, Frith K: Emerging diseases threaten conservation.
Environmental Health Perspectives 111:A506–A507,
2003.
63. Ewalt DR, Payeur JB, Martin BM, et al: Characteristics of a Brucella
species from a bottlenose dolphin (Tursiops truncatus). J Vet
Diagn Invest 6:448–452, 1994.
64. Fair P, Adams J, Mitchum G, et al: Contaminant blubber burdens
in Atlantic bottlenose dolphins (Tursiops truncatus) from two
southeastern US estuarine areas: concentrations and patterns of
PCBs, pesticides, PBDEs, PFCs, and PAHs. Sci Total Environ
408:1577–1597, 2010.
65. Fair PA, Mitchum G, Hulsey TC, et al: Polybrominated diphenyl
ethers (PBDEs) in blubber of free-ranging bottlenose dolphins
(Tursiops truncatus) from two southeast Atlantic estuarine areas.
Arch Environ Contam Toxicol 53:483–494, 2007.
66. Fair PA, Becker PR: Review of stress in marine mammals.
J Aquat Ecosyst Stress Recovery 7:335–354, 2000.
67. Fair PA, Lee H-B, Adams J, et al: Occurrence of triclosan in
plasma of wild Atlantic bottlenose dolphins (Tursiops truncatus)
and in their environment. Environ Pollut 157:2248–54, 2009.
68. Fayer R, Dubey J, Lindsay DS. Zoonotic protozoa: from land to
sea. Trends Parasitol 20(11):531–536, 2004.
69. Fire SE, Wang Z, Leighfield TA, et al: Domoic acid exposure
in pygmy and dwarf sperm whales (Kogia spp.) from southeastern
and mid-Atlantic U.S. waters. Harmful Algae 8:658–664,
2009.
70. Fire SE, Fauquier D, Flewelling LJ, et al: Brevetoxin exposure in
bottlenose dolphins (Tursiops truncatus) associated with Karenia
brevis blooms in Sarasota Bay, Florida. Mar Biol 152:827–834,
2007.
71. Flewelling LJ, Naar JP, Abbott JP, et al: Red tides and marine
mammal mortalities. Nature 435:755–756, 2005.
72. Forcada J, Hammond PS, Aquilar A: Status of the Mediterranean
monk seal Monachus monachus in the western Sahara and
implications of a mass mortality event. Mar Ecol Prog Sev 188:
249–261, 1999.
684 Veterinary Pathology 48(3)
73. Fossi MC, Marsili L, Casini S, et al: Development of new-tools
to investigate toxicological hazard due to endocrine disruptor
organochlorines and emerging contaminants in Mediterranean
cetaceans. Mar Environ Res 62(Suppl):S2000–S2004, 2006.
74. Fossi MC, Casini S, Marsili L: Potential toxicological hazard
due to endocrine-disrupting chemicals on Mediterranean top
predators: state of art, gender differences and methodological
tools. Environ Res 104:174–182, 2007.
75. Foster G, Jahans KL, Reid RJ, Ross HM: Isolation of Brucella
species from cetaceans, seals and an otter. Vet Rec 138:583–
586, 1996.
76. Foster G, MacMillan AP, Godfroid J, et al: A review of Brucella
sp. infection of sea mammals with particular emphasis on isolates
from Scotland. Vet Microbiol 90:563–580, 2002.
77. Foster G, Osterman BS, Godfroid J, et al: Brucella ceti sp. nov.
and Brucella pinnipedialis sp. nov. for Brucella strains with cetaceans
and seals as their preferred hosts. Int J Syst Evol Microbiol
57:2688–2693, 2007.
78. Garner MM, Lambourn DM, Jeffries SJ, et al: Evidence of
Brucella infection in Parafilaroides lungworms in a Pacific harbor
seal (Phoca vitulina richardsii). J Vet Diagn Invest 9:298–
303, 1997.
79. Gee RH, Charles A, Taylor N, et al: Oestrogenic and androgenic
activity of triclosan in breast cancer cells. J Applied Toxicol
28:78–91, 2008.
80. Geraci JR, Anderson DM, Timperi RJ, et al: Humpback whales
(Megaptera novaeangliae) fatally poisoned by dinoflagellate
toxin. Can J Fish Aquat Sci 46:1895–1898, 1989.
81. Glibert PM, Anderson D, Gentien PE, et al: The global, complex
phenomena of harmful algal blooms. Oceanography 18:137–
147, 2005.
82. Goldstein T, Mazet JAK, Zabka TS, et al: Novel symptomatology
and changing epidemiology of domoic acid toxicosis in California
sea lions (Zalophus californianus): an increasing risk to
marine mammal health. Proc R Soc Ser B Biol 275(1632):267–
276, 2008.
83. Goldstein T, Zabka TS, Delong RL, et al: The role of domoic
acid in abortion and premature parturition of California sea
lions (Zalophus californianus) on San Miguel Island, California.
J Wildl Dis 45(1):91–108, 2009.
84. Gonza´lez L, Patterson IA, Reid RJ, et al: Chronic meningoencephalitis
associated with Brucella sp.infection in live-stranded
striped dolphins (Stenella coeruleoalba). J Comp Pathol
126:147–152, 2002.
85. Greig TW, Bemiss JA, Lyon BA, et al: Prevalence and diversity
of antibiotic resistant Escherichia coli in bottlenose dolphins
(Tursiops truncatus) from the Indian River Lagoon, Florida, and
Charleston Harbor area, South Carolina. Aquatic Mammals
33(2):185–194, 2007.
86. Greig DJ, Ylitalo GM, Hall AJ, et al: Transplacental transfer of
organochlorines in California sea lions (Zalophus californianus).
Environ Toxicol Chem 26(1):37–44, 2007.
87. Gulland FMD, Koski M, Lowenstine LJ, et al: Leptospirosis in
California sea lions (Zalophus californianus) stranded along the
central California coast, 1981–1994. J Wildl Dis 32:572–580,
1996.
88. Gulland F: Domoic acid toxicity in California sea lions
(Zalophus californianus) stranded along the central California
coast, May-October 1998. Report to the National Marine
Fisheries Service Working Group on Unusual Marine Mammal
Mortality Events. US Dept Commerce, NOAA Tech. Memo.
2000. NMFS-OPR-17, 45 p.
89. Gulland FM, Haulena M, Fauquier D, et al: Domoic acid toxicity
in California sea lions (Zalophus californianus): clinical signs,
treatment and survival. Vet Rec 150(15):475–480, 2002.
90. Gulland FM, Hall AJ: Is marine mammal health deteriorating?
Trends in the global reporting of marine mammal disease. Eco-
Health 4:135–150, 2007.
91. Hall AJ, Hugunin K, Deaville R, et al: The risk of infection from
polychlorinated biphenyl exposure in the harbor porpoise (Phocoena
phocoena): a case–control approach. Environ Health Perspect
114:704–711, 2006.
92. Hammill MO, Lesage V, Kingsley MC: Cancer in beluga from
the St. Lawrence estuary. Environ Health Perspect 111:A77–
A78, 2003.
93. Hansen L, Schwacke LH, Mitchum GB, et al: Geographic variation
in polychlorinated biphenyl and organochlorine pesticide
concentrations in the blubber of bottlenose dolphins from the
US Atlantic coast. Sci Total Environ 319:147–172, 2004.
94. Harms CA, Maggi RG, Breitschwerdt EB, et al: Bartonella species
detection in captive, stranded and free-ranging cetaceans.
Vet Res 39(6):59, 2008.
95. Herna´ndez-Mora G, Gonza´lez-Barrientos R, Morales JA, et al:
Neurobrucellosis in stranded dolphins, Costa Rica. Emerg Infect
Dis 14(9):1430–1433, 2008.
96. Hoagland P, Jin D, Polansky LY, et al: The costs of respiratory
illnesses arising from Florida Gulf coast Karenia brevis blooms.
Environ Health Perspect 117:1239–1243, 2009.
97. Hoekstra PF, O’Hara TM, Fisk AT, et al: Trophic transfer of persistent
organochlorine contaminants (OCs) within an Arctic
marine food web from the southern Beaufort-Chukchi Seas.
Environ Pollut 124:509–522, 2003.
98. Hoekstra PF, O’Hara TM, Karlsson H, et al: Enantiomer-specific
biomagnification of a-hexachlorocyclohexane and selected
chiral chlordane-related compounds within an Arctic marine
food web. Environ Toxicol Chem 22:2482–2491, 2003.
99. Hoekstra PF, Letcher RJ, O’Hara TM, et al: Hydroxylated and
methylsulfone-containing metabolites of polychlorinated biphenyls
in the plasma and blubber of bowhead whales (Balaena
mysticetus). Environ Toxicol Chem 22:2650–2658, 2003.
100. Hoekstra PF, O’Hara TM, Backus SM, et al: Concentrations of
persistent organochlorine contaminants in bowhead whale tissues
and other biota from northern Alaska: implications for
human exposure from a subsistence diet. Environ Res 98:329–
340, 2005.
101. Houde M, Wells R, Fair P, et al: Polyfluoroalkyl compounds in
free-ranging bottlenose dolphins (Tursiops truncatus) from the
Gulf of Mexico and Atlantic Ocean. Environ Sci Technol
39:6591–6598, 2005.
102. Houde M, Pacepavicus G, Wells R, et al: Polychlorinated biphenyls
and hydroxylated polychlorinated biphenyls in plasma of
bottlenose dolphins (Tursiops truncatus) from the Western
Bossart 685
Atlantic and the Gulf of Mexico. Environ Sci Technol
40(19):5860–5866, 2006.
103. Houde M, Pacepavicius G, Darling C, et al: Polybrominated
diphenyl ethers and their hydroxylated analogs in plasma of bottlenose
dolphins (Tursiops truncatus) from the United States east
coast. Environ Toxicol Chem 28:2061–2068, 2009.
104. Ishibashi H, Matsumura N, Hirano, M, et al: Effects of triclosan
on the early life stages and reproduction of medaka Oryzias
latipes and induction of hepatic vitellogenin. Aquatic Toxicol
67:167–179, 2004.
105. Jahans KL, Foster G, Broughton ES: The characterization of
Brucella strains isolated from marine mammals. Vet Microbiol
57:373–382, 1997.
106. Jenssen BM. Endocrine-disrupting chemicals and climate
change: a worst-case combination for arctic marine mammals
and seabirds? Environ Health Perspect 114:76–80, 2006.
107. Jepson PD, Brew S, MacMillan AP, et al: Antibodies to Brucella
VR in marine mammals around the coast of England and Wales.
Vet Rec 141:513–515, 1997.
108. Jepson PD, Bennett PM, Allchin CR, et al: Investigating potential
associations between chronic exposure to polychlorinated biphenyls
and infectious disease mortality in harbour porpoises from
England and Wales. Sci Total Environ 243/244:339–348, 1999.
109. Jepson PD, Bennett PM, Deaville R, et al: Relationships
between PCBs and health status in UK-stranded harbour porpoises
(Phocoena phocoena). Environ Toxicol Chem 24:238–
248, 2005.
110. Jessup DA, Miller M, Ames J, et al: Southern sea otter as a sentinel
of marine ecosystem health. Ecoheath 1:239–245, 2004.
111. Jessup DA, Miller M, Kreuder-Johnson C, et al: Sea otters in a
dirty ocean. Jour Am Vet Med Assoc 231(11):1648–1652, 2007.
112. Johnson-Restrepo B, Kannan K, Addink R, et al: Polybrominated
diphenyl ethers and polychlorinated biphenyls in a marine
foodweb of coastal Florida. Environmental Science and Technology
39:8243–8250, 2005.
113. Johnson-Restrepo B, Adams DH, Kannan K: Tetrabromobisphenol
(TBBPA) and hexabromocyclododecanes (HBCDs) in tissues
of humans, dolphins, and sharks from the United States.
Chemosphere 70:1935–1944, 2008.
114. Jones KE, Patel NG, Levy MA, et al: Global trends in emerging
infectious disease. Nature 451:990–993, 2008.
115. Kajiwara N, Matsuoka S, Iwata H, et al: Contamination by persistent
organochlorines in cetaceans incidentally caught along
Brazilian coastal waters. Arch Environ Contam Toxicol
46(1):124–134, 2004.
116. Kannan K, Perrotta E, Thomas NJ, et al: A comparative analysis of
polybrominated diphenyl ethers and polychlorinated biphenyls in
Southern sea otters that died of infectious diseases and noninfectious
causes. Arch Environ Contam Toxicol 53(2):293–302, 2007.
117. Kannan K, Perrotta E, Thomas NJ: Association between perfluorinated
compounds and pathological conditions in southern
sea otters. Environ Sci Technol 40(16):4943–4948, 2006.
118. King DP, Hure MC, Goldstein T, et al: Otarine herpesvirus-1: a
novel gammaherpesvirus associated with urogenital carcinoma
in California sea lions (Zalophus californianus). Vet Microbiol
2277:1–7, 2002.
119. Kirkpatrick B, Fleming LE, Squicciarini D, et al: Literature
review of Florida red tide: implications for human health effects.
Harmful Algae 2:99–115, 2004.
120. Krafft A, Lichy JK, Lipscomb TP, et al: Postmortem diagnosis of
morbillivirus infection in bottlenose dolphins (Tursiops truncatus)
in the Atlantic and Gulf of Mexico epizootics by polymerase
chain reaction-based assay. J Wildl Dis 31:410–415, 1995.
121. Kreuder C, Miller M, Jessup DA et al: Patterns of mortality in
the southern sea otter (Enhydra lutris nereis) from 1998–2001.
J Wildl Dis 39:495–509, 2003.
122. Kreuder C, Miller M, Lowenstine LJ, et al: Evaluation of cardiac
lesions and risk factors associated with myocarditis and dilated
cardiomyopathy in southern sea otters (Enhydra lutris nereis).
Am J Vet Res 66:289–299, 2005.
123. Kucklick JR, Struntz WDJ, Becker PR, et al: Persistent organochlorine
pollutants in ringed seals and polar bears collected from
northern Alaska. Sci Total Environ 287:45–59, 2002.
124. Landsberg JH: The effects of harmful algal blooms on aquatic
organisms. Reviews in Fisheries Science 10:113–390, 2002.
125. Lau C, Butenhoff J, Rogers J: The developmental toxicity of perfluoroalkyl
acids and their derivatives. Toxicol Appl Pharmacol
198:231–2341, 2004.
126. Lau C, Anitole C, Hodes D, et al: Perfluoroalkyl acids: a review
of monitoring and toxicological findings. Toxicol Sci 99:366–
394, 2007.
127. Lavery TJ, Butterfield N, Kemper CM, et al: Metals and selenium
in the liver and bone of three dolphin species from South
Australia, 1988–2004. Sci Total Environ 390:77–85, 2008.
128. Lindsay DS, Dubey JP: Long-term survival of Toxoplasma gondii
sporulated oocysts in seawater. J Parasitol 95(4):1019–1020, 2009.
129. Lipscomb TP, Schulman FY, Moffett D, et al: Morbilliviral disease
in Atlantic bottlenose dolphins (Tursiops truncatus) from
the 1987–1988 epizootic. J Wildl Dis 30:567–571, 1994.
130. Lipscomb TP, Kennedy S, Moffett D, et al: Morbilliviral disease
in an Atlantic bottlenose dolphin (Tursiops truncatus) from the
Gulf of Mexico. J Wildl Dis 30:572–576, 1994.
131. Lipscomb TP, Kennedy S, Moffett D, et al: Morbilliviral epizootic
in bottlenose dolphins of the Gulf of Mexico. J Vet Diagn
Invest 8:283–290, 1996.
132. Lipscomb TP, Scott DP, Garber RL, et al: Common metastatic
carcinoma of California sea lions (Zalophus californianus): evidence
of genital origin and association with novel gammaherpesvirus.
Vet Pathol 37(6):609–617, 2000.
133. Lloyd-Smith JO, Greig DJ, Hietala S, et al: Cyclical changes in
seroprevalence of leptospirosis in California sea lions: endemic
and epidemic disease in one host species? BMC Infect Dis
7:125, 2007.
134. Macdonald RW, Barrie LA, Bidleman TF, et al: Contaminants in
the Canadian Arctic: 5 years of progress in understanding
sources, occurrence and pathways. Sci Total Environ 254:
93–234, 2000.
135. Maggi RG, Raverty SA, Lester SJ, et al: Bartonella henselae
in captive and hunter-harvested beluga (Delphinapterus leucas).
J Wildl Dis 44(4):871–877, 2008.
136. Maquart M, Le Fle`che P, Foster G, et al: MLVA-16 typing of
295 marine mammal Brucella isolates from different animal and
686 Veterinary Pathology 48(3)
geographic origins identifies 7 major groups within Brucella ceti
and Brucella pinnipedialis. BMC Microbiol 9:145, 2009.
137. Martineau D, Lagace A, Beland P, et al: Pathology of stranded
beluga whales (Delphinapterus leucas) from the St. Lawrence
estuary, Quebec, Canada. J Comp Pathol 98:287–310, 1988.
138. Martineau D, De Guise S, Fournier M, et al: Pathology and toxicology
of beluga whales from the St. Lawrence estuary, Quebec
Canada. Past, present and future. Sci Total Environ 154:201–
215, 1994.
139. Martineau D, Lair S, De Guise S, Beland P: Intestinal adenocarcinomas
in two beluga whales (Delphinapterus leucas) from the
estuary of the St. Lawrence river. Can Vet J 36:563–565, 1995.
140. Martineau DK, Lemberger A, Dallaire P, et al: Cancer in wildlife,
a case study: beluga from the St. Lawrence Estuary, Quebec,
Canada. Environ Health Perspect 110:285–292, 2002.
141. Martineau DK: Potential synergism between stress and contaminants
in free-ranging cetaceans. International Journal of Comparative
Psychology 20:194–216, 2007.
142. McIlhattan TJ, Martin JW,Wagner RJ, et al: Isolation of Leptospira
pomona from a naturally infected California sea lion,
Sonoma County, California. J Wildl Dis 7:195–197, 1971.
143. McKinney MA, De Guise S, Martineau D, et al: Organohalogen
contaminants and metabolites in beluga whale (Delphinapterus
leucas) liver from two Canadian populations. Environ Toxicol
Chem 25:30–41, 2006.
144. Meites E, Jay MT, Deresinski S, et al: Reemerging leptospirosis,
California. Emerg Infect Dis 10:406–412, 2004.
145. Miller D, Ewing RY, Bossart GD: Emerging and resurging diseases.
In: Marine Mammal Medicine, ed. Dierauf L and Gulland
F, pp. 15–25. CRC Press, Boca Raton, FL, 2001.
146. Miller MA, Miller WA, Conrad PA, et al: Type X Toxoplasma
gondii in a wild mussel and terrestrial carnivores from coastal
California: new linkages between terrestrial mammals, runoff
and toxoplasmosis of sea otters. Int J Parasitol 38(11):1319–
1328, 2008.
147. Miller, MA, Gardner IA, Kreuder C, et al: Coastal freshwater
runoff is a risk factor for Toxoplasma gondii infection of southern
sea otters (Enhydra lutris nereis). Int J Parasitol 32:997–
1006, 2002.
148. Miller AW, Reynolds AC, Sobrino C, et al: Shellfish face uncertain
future in high CO2 world: influence of acidification on
oyster larvae calcification and growth in estuaries. PLoS One
4:e5661, 2009.
149. Miller WG, Adams LG, Ficht TA, et al: Brucella–induced abortions
and infections in bottlenose dolphins (Tursiops truncatus).
J Zoo Wildlife Med 30:100–110, 1999.
150. Mollenhauer MA, Carter BJ, Peden-Adams MM, et al: Gene
expression changes in bottlenose dolphin, Tursiops truncatus,
skin cells following exposure to methylmercury (MeHg) or perfluorooctane
sulfonate (PFOS). Aquat Toxicol 91(1):10–18,
2009.
151. Montie EW, Fair PA, Bossart GD, et al: Cytochrome
P4501A1 expression, polychlorinated biphenyls and hydroxylated
metabolites, and adipocyte size of bottlenose dolphins
from the Southeast United States. Aquat Toxicol 86(3):397–
412, 2008.
152. Montie EW. Pussini N, Schneider GE, et al: Neuroanatomy and
volumes of brain structures of a live california sea lion (Zalophus
californianus) from magnetic resonance images. Anat Rec
292:1523–1547, 2009.
153. Montie EW, Reddy CM, Gebbink WA, et al: Organohalogen
contaminants and metabolites in cerebrospinal fluid and cerebellum
gray matter in short-beaked common dolphins and Atlantic
white-sided dolphins from the western North Atlantic. Environ
Pollut 157:2345–2358, 2009.
154. Moore SE: Marine mammals as ecosystem sentinels. J Mammal
89:534–540, 2008.
155. Moore SE: Long-term environmental change and marine mammals.
In: Marine Mammal Research: Conservation Beyond Crisis,
ed. JE Reynolds III, WF Perrin, RR Reeves, S Montgomery
and TJ Ragen, pp. 137–147. Johns Hopkins University Press,
Baltimore, MD, 2005.
156. Mori C, Morsey B, Levin M, et al: Effects of organochlorines,
individually and in mixtures, on B-cell proliferation in marine
mammals and mice. J Toxicol Environ Health A 71(4):266–
275, 2008.
157. Mos L,Morsey B, Jeffries SJ, et al: Chemical and biological pollution
contribute to the immunological profiles of free-ranging
harbour seals. Environm Toxicol Chem 25:3110–3117, 2006.
158. Mun˜oz PM, Garcı´a-Castrillo G, Lo´pez-Garcı´a P, et al: Isolation
of Brucella species from a live-stranded striped dolphin (Stenella
coeruleoalba) in Spain. Vet Rec 158:450–451, 2006.
159. Murdoch ME, Reif JS, Mazzoil M, et al: Lobomycosis in bottlenose
dolphins (Tursiops truncatus) from the Indian River
Lagoon, Florida: estimation of prevalence, temporal trends, and
spatial distribution. Eco Health 5(3):289–297, 2008.
160. Newman SJ, Smith SA: Marine mammal neoplasia: a review.
Vet Pathol 43:865–880, 2006.
161. Nielsen O, Nielsen K, Stewart REA: Serological evidence of
Brucella spp. Exposure in Atlantic walruses (Odobenus rosmarus
rosmarus) and ringed seals (Phoca hispida) of Arctic
Canada. Arctic 49:383–386, 1996.
162. Nielsen O, Stewart REA, Nielsen K, et al: Serological survey of
Brucella spp. antibodies in some marine mammals of North
America. J Wildlife Dis 37:89–100, 2001.
163. Nielsen O, Nielsen K, Braun R, et al: A comparison of four serologic
assays in screening for Brucella exposure in Hawaiian
monk seals. J Wildl Dis 41(1):126–133, 2005.
164. Nin˜o-Torres CA, Gardner SC, Zenteno-Savı´n T, et al: Organochlorine
pesticides and polychlorinated biphenyls in California
sea lions (Zalophus californianus californianus) from the Gulf
of California, Me´xico. Arch Environ Contam Toxicol
56(2):350–359, 2009.
165. Nollens H, Jacobson E, Gulland FMD, et al: Pathology and preliminary
characterization of a parapoxvirus isolated from a California
sea lion (Zalophus californianus). J Wildl Dis 42(1):23–
32, 2006.
166. Nollens HH, Wellehan JF, Saliki JT, et al: Characterization of a
parainfluenza virus isolated from a bottlenose dolphin (Tursiops
truncatus). Vet Microbiol 128(3–4):231–242, 2008.
167. Norman SA, DiGiacomo RF, Gulland FM, et al: Risk factors for
an outbreak of leptospirosis in California sea lions (Zalophus
Bossart 687
californianus) in California, 2004. J Wildl Dis 44(4):837–844,
2008.
168. O’Hara TM, Hoekstra PF, Hanns C, et al: Concentrations of
selected persistent organochlorine contaminants in store-bought
foods from northern Alaska. Int J Circumpolar Health 64:
303–313, 2005.
169. Ohishi K, Zenitani R, Bando T, et al: Pathological and serological
evidence of Brucella infection in baleen whales (Mysticeti)
in the western North Pacific. Comp Immunol Microb 26:
125–136, 2003.
170. Orvos DR, Versteeg DJ, Inauen J, et al: Aquatic toxicity of triclosan.
Environ Toxicol Chem 21:1338–1349, 2002.
171. O’Shea TJ: Environmental contaminants and marine mammals.
In: Biology of Marine Mammals, ed. Reynolds JE, Rommel SA,
pp. 485–563. Smithsonian Institution, Washington, DC, 1999.
172. O’Shea TJ, Bossart GD, Fournier M, et al: Conclusions and perspectives
for the future. In: Toxicology of Marine Mammals, ed.
Vos JG, Bossart GD, Fournier M and O’Shea T, pp. 595–613.
Taylor & Francis, London, 2003.
173. O’Shea TJ, Tanabe S: Persistent ocean contaminants and marine
mammals: a retrospective overview. In: Toxicology of Marine
Mammals, ed. Vos JG, Bossart GD, Fournier M and O’Shea T,
pp. 99–134. Taylor & Francis, London, 2003.
174. Perrett LL, Brew SD, Stack JA, et al: Experimental assessment
of the pathogenicity of Brucella strains from marine mammals
for pregnant sheep. Small Rumin Res 51:221–228, 2004.
175. Porte C, Janer G, Lorusso LC, et al: Endocrine disruptors in
marine organisms: approaches and perspectives. Comp Biochem
Physiol C Toxicol Pharmacol 143(3):303–315, 2006.
176. Prenger-Berninghoff E, Siebert U, Stede M, et al: Incidence of
Brucella species in marine mammals of the German North Sea.
Dis Aquat Organ 81(1):65–71, 2008;.
177. Raga JA, Banyard A, Domingo M, et al: Dolphin morbillivirus
epizootic resurgence, Mediterranean Sea. Emerg Infect Dis
14(3):471–473, 2008.
178. Ramsdell JS, Muha N: Acute domoic acid poisoning in rats leads
to a chronic syndrome of aggressive behavior and epilepsy. Fifth
Symposium on Harmful Algae in the U.S. Ocean Shores,
Washington, DC, 2009, p. 68.
179. Ramsdell JS: The molecular and integrative basis to domoic acid
toxicity. In: Phycotoxins: Chemisty and Biochemistry, ed.
Botana L, pp. 223–250. Blackwell, Ames, IA, 2007.
180. Ramsdell JS, Zabka TS: In utero domoic acid toxicity: a fetal
basis to adult disease in the California sea lion (Zalophus californianus).
Mar Drugs 6(2):262–290, 2008.
181. Randolph SE: Perspectives on climate change impacts on infectious
diseases. Ecology 90:927–931, 2009.
182. Rector A, Bossart GD, Ghim SJ, et al: Characterization of a
novel close-to-root papillomavirus from a Florida manatee by
using multiply primed rolling-circle amplification: trichechus
manatus latirostris papillomavirus type 1. J Virol 78:12698–
12702, 2004.
183. Rector A, Stevens H, Lacave G, et al: Genomic characterization
of novel dolphin papillomaviruses provides indications for
recombination within the Papillomaviridae. Virology 378:
151–161, 2008.
184. Reddy ML, Dierauf LA, Gulland FMD: Marine mammals as
sentinels of ocean health. In: Marine Mammal Medicine, ed.
Dierauf L and Gulland F, pp. 3–13. CRC Press, Boca Raton,
FL, 2001.
185. Rehtanz M, Ghim S-J, Rector A, et al: Isolation and
characterization of the first American bottlenose dolphin papillomavirus:
Tursiops truncatus papillomavirus type 2. J Gen Virol
87:3559–3565, 2006.
186. Rehtanz M, Bossart GD, Doescher B, et al: Bottlenose dolphin
(Tursiops truncatus) papillomaviruses: Vaccine antigen candidates
and screening test development. Vet Microbiol. 2008.
doi:10.1016/j.vetmic.2008.06.017.
187. Rehtanz M, Ghim S, McFee W, et al: Papillomavirus antibody
prevalence in free-ranging and captive bottlenose dolphins
(Tursiops truncatus). J Wildl Dis 46:136–145, 2010.
188. Reif JS, Peden-Adams MM, Romano TA, et al: Immune dysfunction
in Atlantic bottlenose dolphins (Tursiops truncatus)
with lobomycosis. Med Mycol 4:1–11, 2008.
189. Reif JS, Mazzoil M, McCulloch SD, et al: Lobomycosis in
Atlantic bottlenose dolphins (Tursiops truncatus) from the
Indian River Lagoon, Florida. J Am Vet Med Assoc 228:
104–108, 2006.
190. Reijnders PJH: Reproductive failure in common seals feeding on
fish from polluted coastal waters. Nature 324:456–457, 1986.
191. Retamal P, Blank O, Abalos P, et al: Detection of anti-Brucella
antibodies in pinnipeds from the Antarctic territory. Vet Rec
146:166–167, 2000.
192. Rhyan JC, Spraker TR: Emergence of diseases from wildlife
reservoirs. Vet Pathol 47(1):34–39; 2010.
193. Robertson LW, Hansen LJ: PCBs: Recent Advances in Environmental
Toxicology and Health Effects. University Press of
Kentucky, Lexington, KY, 2001.
194. Ross HM, Foster G, Reid RJ, et al: Brucella species infection in
sea-mammals. Vet Rec 134:359–364, 1994.
195. Ross HM, Jahans KL, MacMillan AP, et al: Brucella species
infection in North Sea seal and cetacean populations. Vet Rec
138:647–648, 1996.
196. Ross P, De Swart RL, Addison R, et al: Contaminant-induced
immunotoxicity in harbour seals: wildlife at risk? Toxicology
112:157–169, 1996.
197. Ross PSR: The role of immunotoxic environmental contaminants
in facilitating the emergence of infectious diseases in
marine mammals. HERA 8:277–292, 2002.
198. Rotstein DS, Burdett LG, McLellan W, et al: Lobomycosis
in offshore bottlenose dolphins (Tursiops truncatus), North
Carolina. Emerg Infect Dis 15(4):588–590, 2009.
199. Rubin CH, Lanier A, Socha M, et al: Exposure to persistent organochlorines
among Alaska Native women. Int J Circumpolar
Health 60:157–169, 2001.
200. Sandau CD, Ayotte P, Dewailly E, et al: Analysis of hydroxylated
metabolites of PCBs (OH-PCBs) and other chlorinated
phenolic compounds in whole blood from Canadian Inuit.
Environ Health Perspect 108:611–616, 2000.
201. Schaefer AM, Reif JS, Goldstein JD, et al: Serological evidence
of exposure to selected pathogens in free-ranging Atlantic bottlenose
dolphins (Tursiops truncatus) from the Indian River
688 Veterinary Pathology 48(3)
Lagoon, Florida and Charleston, South Carolina. Aquatic Mammals
35:163–170, 2009.
202. Schaefer AM, Goldstein JD, Reif JS, et al: Antibiotic-resistant
organisms cultured from Atlantic bottlenose dolphins (Tursiops
truncatus) inhabiting estuarine waters of Charleston, SC and
Indian River Lagoon, FL. EcoHealth. 2009. doi:10.1007/
s10393-009-0221-5.
203. Scholin CA, Gulland F, Doucette GJ, et al: Mortality of sea lions
along the central California coast linked to a toxic diatom bloom.
Nature 403(6765):80–84, 2000.
204. Schulman FY, Lipscomb TP, Moffett D, et al: Histologic, immunohistochemical,
and polymerase chain reaction studies of
bottlenose dolphins from the 1987-1988 United States Atlantic
coast epizootic. Vet Pathol 34:288–295, 1997.
205. Silvagni PA, Lowenstine LJ, Spraker T, et al: Pathology of
domoic acid toxicity in California sea lions (Zalophus californianus).
Vet Pathol 42(2):184–191, 2005.
206. Slenning BD: Global climate change and implications for
disease emergence. Vet Path. 47:28–33, 2010.
207. Sohn AH, Probert WS, Glaser CA, et al: Human neurobrucellosis
with intracerebral granuloma caused by a marine mammal
Brucella spp. Emerg Infect Dis 9:485–488, 2003.
208. Stavros H-CW, Bossart GD, Hulsey TC, et al: Trace element
concentrations in blood of free-ranging bottlenose dolphins
(Tursiops truncatus): influence of age, sex and location. Mar
Pollut Bull 56:348–379, 2008.
209. Stavros H-CW, Bossart GD, Hulsey TC, et al: Trace element
concentrations in skin of free-ranging bottlenose dolphins
(Tursiops truncatus) from the southeast Atlantic coast. Sci Total
Environ 388:300–315, 2007.
210. Stein JE, Tilbury KL, Meador JP, et al: Ecotoxicological
investigations of bottlenose dolphin (Tursiops truncatus) strandings:
accumulation of persistent organic chemicals and metals.
In: Toxicology of Marine Mammals, ed. Vos JG, Bossart GD,
Fournier M and O’Shea T, pp. 458–85. Taylor & Francis,
London, 2003.
211. Stoddard RA, Atwill ER, Gulland FMD, et al: Risk factors for
infection with pathogenic and antimicrobial-resistant fecal bacteria
in northern elephant seals in California. Public Health Rep
123:360–370, 2008.
212. Stone DA: Predicted climate changes for the years to come
and implications for disease impact studies. Rev Sci Tech 27:
319–330, 2008.
213. Tabuchi M, Veldhoen N, Dangerfield N, et al: PCB-related
alteration of thyroid hormones and thyroid hormone receptor
gene expression in free-ranging harbor seals (Phoca vitulina).
Environ Health Perspect 114(7):1024–1031, 2006.
214. Tachibana M, Watanabe K, Kim S, et al: Antibodies to Brucella
spp. in Pacific bottlenose dolphins from the Solomon Islands.
J Wildl Dis 42(2):412–414, 2006.
215. Tanabe S, Iwata H, Tatsukawa R: Global contamination by persistent
organochlorines and their ecotoxicological impact on
marine mammals. Sci Total Environ 154:163–177, 1994.
216. Tanabe S: Contamination and toxic effects of persistent endocrine
disrupters in marine mammals and birds. Mar Pollut Bull
45:69–77, 2002.
217. Taubenberger JK, Tsai MM, Atkin TJ, et al: Molecular
genetic evidence of a novel morbillivirus in a long-finned
pilot whale (Globicephalus melas). Emerg Infect Dis 6:
42–45, 2000.
218. Taylor LH, Latham SM, Woolhouse MEJ: Risk factors for
human disease emergence. Phil Trans R Soc Lond B 356:
983–989, 2001.
219. Tiedeken JA, Ramsdell JS: DDT exposure of zebrafish embryos
enhances seizure susceptibility: relationship to fetal p,p0-dde
burden and domoic acid exposure of california sea lions. Environ
Health Perspect 117:68–73, 2009.
220. Trainer VL, Baden DE: High affinity binding of red tide neurotoxins
tomarinemammal brain.Aquatic Toxicol 46(2):139–148, 1999.
221. Tryland M, Kleivane L, Alfredson A, et al: Evidence of Brucella
infection in marine mammals in the North Atlantic Ocean. Vet
Rec 144:588–592, 1999.
222. Tuerk KJS, Kucklick R, Becker PR, et al: Persistent organic pollutants
in two dolphin species with focus on toxaphene and polybrominated
diphenyl ethers. Environmental Science and
Technology 39:692–698, 2005.
223. Van Bressem M-F, Visser IG, Van De Bildt MG, et al: Morbillivirus
infection in Mediterranean striped dolphins (Stenella
coeruleoalba). Vet Rec 129:471–472, 1991.
224. Van Bressem M-F, van Waerebeek K, Raga JA, et al: Serological
evidence of Brucella species in odontocetes from the south
Pacific and the Mediterranean. Vet Rec 148:657–661, 2001.
225. Van Bressem M-F, Waerebeek KV, Jepson PD, et al: An insight
into the epidemiology of dolphin morbillivirus worldwide. Vet
Microbiol 81(4):287–304, 2001.
226. Van Bressem MF, Raga JA, Di Guardo G, et al: Emerging
infectious diseases in cetaceans worldwide and the possible
role of environmental stressors. Dis Aquat Organ 86(2):
143–157, 2009.
227. Van Dolah FM, Douchette GJ, Gulland F, et al: Impacts of algal
toxins on marine mammals. In: Toxicology of Marine Mammals,
ed. Vos JG, Bossart GD, Fournier M and O’Shea T, pp.
247–270. Taylor & Francis, London, 2003.
228. Vedros NA, SmithAW, Schonewa J, et al: Leptospirosis epizootic
among California sea lions. Science 172:1250–1251, 1971.
229. Veldhoen N, Skirrow RC, Osachoff H, et al: The bactericidal
agent triclosan modulates thyroid-associated gene expression
and disrupts postembryonic anuran development. Aquatic Toxicol
80:217–227, 2006.
230. Venn-Watson S, Rivera R, Smith CR, et al: Exposure to novel
parainfluenza virus and clinical relevance in 2 bottlenose
dolphin (Tursiops truncatus) populations. Emerg Infect Dis
14(3):397–405, 2008.
231. Vetter W, Turek C, Marsh G, et al: Identification and quantification
of new polybrominated dimethoxybiphenyls (PBDMBs)
in marine mammals from Australia. Chemosphere 73(4):
580–586, 2008.
232. Visser IKG, Van Bressem M-F, de Swart RL, et al: Characterization
of morbilliviruses isolated from dolphins and porpoises in
Europe. J Gen Virol 74:631–641, 1993.
233. Walsh CJ, Luer CA, Noyes DR: Effects of environmental
stressors on lymphocyte proliferation in Florida manatees,
Bossart 689
Trichechus manatus latirostris. Veterinary Immunology and
Immunopathology 103:247–256, 2005.
234. Wells RS, Rhinehart HL, Hansen LJ, et al: Bottlenose dolphins
as marine ecosystem sentinels: developing a health monitoring
system. EcoHealth 1:246–254, 2004.
235. Whatmore AM, Dawson C, Groussaud P, et al: A marine
mammal Brucella genotype associated with zoonotic infection.
Emerg Inf Dis 14:517–518, 2008.
236. Woshner VM, O’Hara TM, Bratton GR, et al: Concentrations
and interactions of selected essential and non-essential elements
in ringed seals and polar bears of Arctic Alaska. J Wildl Dis
37:711–721, 2001.
237. Woshner V,Knott K,Wells R, et al:Mercury and seleniumin blood
and epidermis of bottlenose dolphins (Tursiops truncatus) from
Sarasota Bay, FL: interaction and relevance to life history and
hematologic parameters. EcoHealth 5(3): 360–370, 2008.
238. Ylitalo, GM, Stein JE, Hom T, et al: The role of organochlorines
in cancer-associated mortality in California sea lions (Zalophus
californianus). Mar Pollut Bull 50:30–39, 2005.
239. Zabka TS, Goldstein T, Cross C, et al: Characterization of a
degenerative cardiomyopathy associated with domoic acid toxicity
in California sea lions (Zalophus californianus). Vet Pathol
46(1):105–119, 2009.
240. Zegers BN, Mets A, Van Bommel R, et al: Levels of hexabromocyclododecane
in harbor porpoises and common dolphins from
western European seas, with evidence for stereoisomerspecific
biotransformation by cytochrome p450. Environ Sci
Technol 39(7):2095–2100, 2005.
690 Veterinary Pathology 48(3)