Despite their ban, polybrominated diphenyl ethers (PBDEs) are frequently detected in various environmental compartments including marine and coastal ecosystems due to their persistence, bio-accumulative, high production volumes, and widespread use. One of the major concerns from PBDEs is the transformation products, such as hydroxylated polybrominated diphenyl ethers (OH-BDEs), which are more bioactive than the parent compounds. For example, 6-hydroxy-2,2',4',4-tetrabromodiphenyl ether (6-OH-BDE-47) is a typical metabolite of PBDEs and cause endocrine system disruption, developmental toxicity, and neurotoxicity in different species. Despite being widely detected in marine environments, investigations on the toxicological mechanisms of 6-OH-BDE-47 in cetaceans remain scarce. High concentrations of PBDEs accumulate in cetaceans due to the long lifespan and large fat reserve. The accumulated PBDEs have become the major source of OH-BDEs in cetaceans. We exposed immortalized fibroblast cell lines from the skin of pygmy killer whales (PKW-LWHT) and Indo-Pacific finless porpoises (FP-LWHT) to 6-OH-BDE-47 and analyzed changes in cellular function using transcriptomic data, along with enzymatic activity. Exposure to the body-relevant body burdens of 6-OH-BDE-47 (250 and 500 ng mL