Background: Developments of pulmonary diseases, often accompanied by infections of bacteria, severely affect meat production and welfare of pigs. This study investigated the association of lung lesions and Mycoplasma levels inferred from 16S rRNA sequencing of bronchoalveolar lavage fluid with 57 immune cells and 25 hematological traits in 307 pigs at age of 240 days from an eight-breed heterogeneous cross.Result: At a false discovery rate threshold of 0.05, we found that the greater severity of lung lesions were significantly associated with higher CD8+ to CD3+ cell ratio (CD8+/CD3+), neutrophil to lymphocyte ratio (NLR), and standard deviation of red blood cell volume distribution width (RDW-SD), and lower CD4-CD8-/CD3+, CD3+CD4-CD8-/PBMCs, CD14-CD16-/PBMCs, mean corpuscular hemoglobin concentration (MCHC), lymphocyte count (LYM) and lymphocyte count percentage (LYMR), reflected an status of inflammation, immune suppression and hypoxia of the pigs accompanying the development of the lung lesion. The Mycoplasma abundance showed positive correlations with neutrophil count (NEU), neutrophil count percentage (NEUR), neutrophil-to-lymphocyte ratio (NLR), monocyte count (MON), RDW-CV, and RDW-SD, and negative correlations with MCHC, LYM, and LYMR, these correlations are largely consistent with those of lung lesions, supporting the comorbidity of lung lesions and Mycoplasma infection. We also observed a nonlinear association that the sharp increases in NEU and NEUR occurred only when Mycoplasma abundance raised to a level above the population-average. Conclusion: This study showed that the pigs from an eight-breed cross heterogeneous population reared under standardized housing conditions suffered lesion averagely covered 40% of lung, and the lung lesions were significantly linked to load of Mycoplasma in bronchoalveolar lavage fluid. We further demonstrated that the lung lesion and load of Mycoplasma perturb a large variety of immune and hematological traits. These associations provide helpful insights into the changes of host immune status in response to mycoplasma relevant lung diseases in pigs.