| Summary: | Marine bivalves are rich in docosahexaenoic acid (DHA), a polyunsaturated fatty acid known to be beneficial for human health; however, the potential role of DHA in protecting shellfish from the toxicity of diarrhetic shellfish toxins (DSTs) remains poorly understood. Here, we aimed to study the effect of DHA on the response of the bivalve, <i>Perna viridis</i>, to DSTs by using LC-MS/MS, RT-qPCR, and histological examination. In this study, we observed that the DHA content decreased significantly with esterification of DSTs in the digestive gland of the mussel <i>P. viridis</i> after 96 h of exposure to <i>Prorocentrum lima</i>, a DST-producing dinoflagellate. The addition of DHA significantly increased the esterification level of DSTs and increased the expression of Nrf2 signaling pathway-related genes and enzyme activities, alleviating the damage of DSTs to digestive glands. These results suggested that DHA may mediate the esterification of DSTs and activation of the Nrf2 signaling pathway in <i>P. viridis</i> to protect mussels from the toxic effects of DSTs. This study may provide new insights regarding the response of bivalves to DSTs and lay the foundation for uncovering the role of DHA in environmental adaptation of bivalves.
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