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Levels of amino acids and energy substances, such as l-proline, isoleucine, and fructose, were higher in the gill of the S35 group. The combination of transcriptomic and metabolomic data indicated that metabolism of amino acids, carbohydrates, and lipids was enhanced in the gill during adaptation to high salinity. These results clarified the complex physiological processes involved in the response to hyperosmotic stress and maintenance of metabolism in the gill of razor clams. These findings provide a reference for further study of the