AbstractTo clarify the genetic influence of mycoplasmal pneumonia of swine (MPS) lesion‐selected Landrace (La) on MPS resistance and immune characteristics in three‐way crossbred pigs (LaWaDa), the LaWaDa pigs were compared with the non‐selected crossbred (LbWbDb) and purebred (La) pigs. The MPS lesion score in the three lines was as follows: La line < LaWaDa line < LbWbDb line, with significant differences among the lines. The proportions of myeloid cells and T cells were lower and higher, respectively, in the LaWaDa pigs compared with those in the other two lines. Messenger RNA (mRNA) expression of interleukin (IL)‐6, IL‐10, transforming growth factor‐β, and interferon‐γ in peripheral blood was significantly increased after vaccination in the La and LaWaDa lines. IL‐4 mRNA expression in the LaWaDa line was intermediate to the La and LbWbDb lines. Furthermore, principal component analysis for immune traits and MPS lesions was executed to clarify the characteristics of each pig line. These findings suggest that the immune responses in the three pig lines are genetically distinct and that MPS resistance and some immunity characteristics from the La line were transmitted to the three‐way crossbred pigs.