A novel potential toxic target of PBDEs in cetaceans: Impaired wound healing demonstrated in Indo-Pacific finless porpoise fibroblasts.

Cetaceans, particularly those inhabiting coastal areas, face compounding threats from diverse anthropogenic activities, including vessel strikes, entanglement, and pollution. However, these stressors have predominantly been assessed in isolation, overlooking the potential synergistic effects arising from their frequent co-occurrence. Polybrominated diphenyl ethers (PBDEs), a class of toxic flame retardants ubiquitous in marine environments, bioaccumulate in cetaceans posing significant health risks. This study provides the first integrated mechanistic insight into how PBDE exposure not only directly compromises cetacean health but also amplifies the impacts of other anthropogenic pressures. Specifically, PBDE exposure significantly delays cetacean wound healing by impairing skin fibroblast migration, reducing wound closure rates by 5.6-7.6 % compared with controls. Critically, PBDEs downregulate type I and VI collagen expression at the protein level by 13-19 % and 27-36 %, respectively, and inhibit TGF-β1-driven cell transition via suppression of SMAD2 phosphorylation, reducing p-SMAD2 levels by 45-65 %, thereby disrupting extracellular matrix (ECM) expression and impeding cellular migration. The findings demonstrate that PBDEs impair wound healing in cetaceans by disrupting ECM remodeling through dual inhibition of collagen homeostasis and the TGF-β1/Smad signaling pathway. Considering that risk of injuries is increasing due to increase in fishing and transportation vessels, the delayed wound healing induced by pollutants such as PBDEs may increase mortality in cetacean populations. This work highlights the critical need for integrated risk assessments of multiple stressors in cetacean conservation, particularly for coastal species such as the Indo-Pacific finless porpoise and other cetaceans burdened with high PBDEs concentrations.