Global ecosystems are experiencing rapid human-induced environmental changes. The marine environment is influenced by a wide variety of anthropogenic stressors, including chemical runoff and sound pollution. While stressors may not be lethal to marine wildlife in isolation, an increase in the number and magnitude of stressors reduces individual fitness and increases vulnerability to other stressors, such as the effects of global climate change and infectious diseases. As such, it is increasingly important to understand the physiological impacts of anthropogenic and natural stressors on marine wildlife. Marine mammals are known sentinels of ocean health and provide an excellent model system to investigate the health effects of anthropogenic and natural stressors on long-lived mammals. Traditional approaches to marine mammal health assessment have limited applicability in wild populations of conservation concern as they often rely on serum, which is not obtainable from most species in situ. However, novel integration of molecular methods that can be applied to routinely collected biopsies composed of skin and blubber will expand our capacity for health assessment in wild cetacean populations and further our understanding of the mechanistic relationship between stressors and possible sublethal effects. I integrated well established molecular tools in new ways in order to investigate the potential impacts of anthropogenic contaminants and environmental variation on wild cetaceans in the Southern California Bight (SCB). Combining non-targeted contaminant analysis with blubber endocrine biomarkers in chapter one provided evidence of bioaccumulation and endocrine disruption related to halogenated organic contaminants (HOCs) in short-beaked common dolphins (Delphinus delphis). Higher levels of several anthropogenic and previously uncharacterized compounds were associated with lower testosterone levels in mature D. delphis highlighting the potential for reproductive effects due to exposure. Chapter two explores sources of transcriptomic variation related to sea surface temperature, geographic location, ecotype, sex, and pregnancy in SCB bottlenose dolphins (Tursiops truncatus). A large proportion of skin transcriptomic expression was linked to sea surface temperature with a smaller proportion explained by sex. Additional unexplained variation was identified between geographic locations and genetic ecotype, including lower expression of immune genes within a coastal T. truncatus ecotype compared to the offshore ecotype. Chapter three further examines whether the unexplained transcriptomic variation from chapter two is related to HOC exposure in both the coastal and offshore T. truncatus ecotypes. This research identified patterns of HOC exposure and the potential effects in both ecotypes and indicated the coastal ecotype may be more vulnerable to HOC related health impacts. These findings highlight the need for additional efforts to understand the mechanistic relationship between stressors, in particular HOCs, and their physiological effects in southern California marine mammals and to identify the potential population level impacts of exposure on marine wildlife.