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Microplastics (MPs) are ubiquitous pollutants that have potentially harmful and toxic effects. MPs are frequently ingested by aquatic animals, as microplastics share a similar size and color to their food. Heavy metals are harmful and difficult to degrade, have a wide range of sources and an extended residual time from exposure to recovery. Although the effects of MPs and heavy metals on the performance of aquatic species have been extensively studied, the molecular mechanisms of MP and heavy metal (Pb, Cd and Cu) exposure on aquatic organisms remain unclear. Here, the effects of MPs and heavy metal accumulation on the line seahorse, <i>Hippocampus erectus</i>, were investigated at the molecular level using transcriptome analysis. Using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, we found that immune, metabolic, and apoptotic pathways were affected in the heavy metal group, whereas the DNA damage repair and metabolism pathways were mainly involved in the MP group. Both types of stress caused significant changes in the genes related to the antioxidant pathway in <i>H. erectus</i> larvae. Transcriptome differences between the treatment groups were analyzed, and sensitive candidate genes (<i>Hsp70</i>, <i>Hsp90</i>, <i>Sod</i>, etc.) were screened. The response characteristics of seahorses to MP environmental stress were also investigated. Using seahorse as a biological model and candidate sensitive genes as a basis, our results provide a theoretical basis for detecting MPs and heavy metals pollution in coastal areas.