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With the tolerance of flooding and strong winds, <i>Taxodium</i> has been widely recognized as an ecologically important tree in China. Red blight disease, caused by the fungal pathogen <i>Pestalotiopsis maculans</i>, is known as one of the most severe leaf diseases of <i>Taxodium</i>. However, limited information is available regarding the host plant defense response to this pathogen. To uncover the mechanism of the plant–pathogen interaction, we performed an essential comparative transcriptome analysis of the resistant species <i>T. distichum</i> and susceptible species <i>T. mucronatum</i> after <i>P. maculans</i> infection. A total of 50,763 unigenes were assembled, of which 34,651 unigenes were annotated in eight public databases. Differentially expressed gene (DEG) analysis identified 3420 and 4414 unigenes in response to infection in <i>T. distichum</i> and <i>T. mucronatum</i>, respectively. The transcriptome analysis exhibited differential expression patterns in the two species in response to the infection. Moreover, this study first found that, compared to susceptible <i>T. mucronatum</i>, <i>T. distichum</i> can effectively perceive the invasion of <i>P. maculans</i> and make a valid response through SA signal pathway. These data provided not only new insights into the resistance mechanisms in the highly resistant species but also promising genetic resources for improving the fungal pathogen tolerance in <i>Taxodium</i> breeding.