Cetaceans in the Southern California Bight (SCB) are exposed to high levels of halogenated organic contaminants (HOCs), which have previously been linked to impaired reproductive health and immune responses. We used a combination of molecular tools to examine the potential physiological impacts of HOC exposure in two bottlenose dolphin ( Tursiops truncatus) ecotypes in the SCB. We quantified 25 HOCs in the blubber of 22 biopsies collected from males between 2012 and 2016. We then analyzed genome-wide gene expression in skin using RNA-sequencing and measured blubber testosterone to compare HOC exposure with cellular and endocrine biomarkers. We found high levels of HOCs in both ecotypes with significantly higher total polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), tris(4-chlorophenyl)methanol (TCPMOH), and chlordane-related compounds in the coastal ecotype versus the offshore ecotype. We found evidence of PBDE bioaccumulation in both ecotypes, however, the pattern of bioaccumulation or endocrine disruption for other HOCs was different between the ecotypes, suggesting potential endocrine disruption in the coastal ecotype. We also observed correlations between HOCs and gene coexpression networks enriched for xenobiotic metabolism, hormone metabolism, and immune response that could indicate cellular effects from HOC exposure. By integrating measurements of HOC load with both transcriptome profiling and endocrine biomarkers, our approach provides insight into HOC exposure and potential impacts on wild cetacean health in southern California.