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Through excellent absorption and transformation, the macrophyte Myriophyllum (M.) aquaticum can considerably remove phosphorus from wastewater. The results of changes in growth rate, chlorophyll content, and roots number and length showed that M. aquaticum could cope better with high phosphorus stress compared with low phosphorus stress. Transcriptome and differentially expressed genes (DEGs) analyses revealed that, when exposed to phosphorus stresses at various concentrations, the roots were more active than the leaves, with more DEGs regulated. M. aquaticum also showed different gene expression and pathway regulatory patterns when exposed to low phosphorus and high phosphorus stresses. M. aquaticum's capacity to cope with phosphorus stress was maybe due to its improved ability to regulate metabolic pathways such as photosynthesis, oxidative stress reduction, phosphorus metabolism, signal transduction, secondary metabolites biosynthesis, and energy metabolism. In general, M. aquaticum has a complex and interconnected regulatory network that deals efficiently with phosphorus stress to varying degrees. This is the first time that the mechanisms of M. aquaticum in sustaining phosphorus stress have been fully examined at the transcriptome level using high-throughput sequencing analysis, which may indicate the direction of follow-up research and have some guiding value for its future applications. [ABSTRACT FROM AUTHOR]