Sesuvium portulacastrum has a strong salt tolerance and can grow in saline and alkaline coastal and inland habitats. This study investigated the physiological and molecular responses of S. portulacastrum to high salinity by analyzing the changes in plant phytohormones and antioxidant activity, including their differentially expressed genes (DEGs) under similar high-salinity conditions. High salinity significantly affected proline (Pro) and hydrogen peroxide (H₂O₂) in S. portulacastrum seedlings, increasing Pro and H₂O₂ contents by 290.56 and 83.36%, respectively, compared to the control. Antioxidant activities, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), significantly increased by 83.05, 205.14, and 751.87%, respectively, under high salinity. Meanwhile, abscisic acid (ABA) and gibberellic acid (GA₃) contents showed the reverse trend of high salt treatment. De novo transcriptome analysis showed that 36,676 unigenes were matched, and 3,622 salt stress-induced DEGs were identified as being associated with the metabolic and biological regulation processes of antioxidant activity and plant phytohormones. POD and SOD were upregulated under high-salinity conditions. In addition, the transcription levels of genes involved in auxin (SAURs and GH3), ethylene (ERF1, ERF3, ERF114, and ABR1), ABA (PP2C), and GA₃ (PIF3) transport or signaling were altered. This study identified key metabolic and biological processes and putative genes involved in the high salt tolerance of S. portulacastrum and it is of great significance for identifying new salt-tolerant genes to promote ecological restoration of the coastal strand.

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