Paragonimiasis (pulmonary fluke disease) is a foodborne parasitic disease caused by trematode infections. Paragonimus proliferus is a characteristic Paragonimus species that was first identified in Yunnan Province of China. No direct evidence has yet proven that P. proliferus can infect humans. However, we previously found that P. proliferus infects and damages rat lung tissues via an unclear mechanism. Here, we infected Sprague Dawley rats with P. proliferus and sequenced their lung transcriptomes at various intervals thereafter. We detected P. proliferus on the surface of rat lung tissues at 7 days post infection. It colonized by attaching and secreting dsRNA and utilized nutrients from the lung tissues for mitosis and meiosis and the dynein arm of lung tissues to develop symmetrical organs. The rats generated different types of immune responses that differed according to the stage of infection. We then analyzed P. proliferus responses to these immune strategies and the genes expressed during each stage of infection. Our findings provide a foundation for developing medical treatments for P. proliferus infection.AJTR Copyright © 2022.