It was found that Vibrio splendidus could survive under high concentration of tetracycline, and the coelomic fluid of sea cucumber increased the tolerance of Vibrio splendidus to tetracycline. Therefore, the transcriptome was determined to find the cause of drug resistance in Vibrio splendidus. Overall design: Vibrio splendidus at three culture stages included OD600=0.6,1.2,2.0. Tetracycline was treated with 10 times minimum inhibitory concentration at 28 ° C for 4 hours. For the coelomic fluid, it was pretreated for 1 h and then exposed to tetracycline for 4 h at 28 ° C