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Liza haematocheila is exposed to various chemical contaminants from anthropogenic sources, including tributyltin chloride (TBTC). Yet the toxicity mechanism of TBTC on haarder remains unclear. The haarder was exposed to different doses (0, 10%, 20%, and 50% of LC 50 -96 h) of TBTC. In this study, the results revealed its high bioaccumulation in the livers and significant alteration for development. The activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase decreased after 96-h exposure to TBTC, this accompanied by an increased malondialdehyde level. TBTC exposure caused the intense production of reactive oxygen species, a reduction in total blood cell count in serum, and apoptosis-related alterations in livers, indicating that enhanced oxidative stress occurred in the process of TBTC exposure. Histological results revealed angiorrhexis and infiltration of inflammatory cells, vacuolar degeneration of hepatocytes in the livers, and swelling, fusion, and disintegration of gill organs. Interestingly, the obtained transcriptional profiles indicated that high doses of TBTC caused energy disorder, apoptosis, and adipogenesis restriction mediated by cytokines and adipokines in Jak-STAT and adipocytokine signaling pathways. In summary, acute exposure to high doses of TBTC could impair the antioxidant system and pathways related to energy, apoptosis and adipogenesis, eventually posing a serious challenge to the fitness of haarder individuals and its fish populations as marine resources. [Display omitted] • Tributyltin chloride (TBTC) bioaccumulated highly in haarder livers. • Apoptosis was induced by TBTC in haarder livers. • TBTC caused transcriptome changes in haarder livers. • TBTC caused energy disorder and adipogenesis restriction in haarder. [ABSTRACT FROM AUTHOR]