Lychee (Litchi chinensis Sonn.) is an economically important tropical fruit threatened by litchi downy blight, caused by the oomycete Peronophythora litchii. To prioritize genes and regulatory features associated with early host responses, we reanalyzed public leaf RNA-seq data from Guiwei and Yurong cultivars (GSE201243; mock and inoculated samples, three biological replicates per group). Differential-expression analysis identified 17 significant DEGs in Guiwei and 117 in Yurong at adjusted P < 0.05, suggesting a broader transcriptional response in Yurong. Eighteen highly responsive genes were selected for structural, motif, promoter, and candidate interaction analyses. These candidates included annotations associated with defense or stress responses, including jacalin-like lectin, pathogenesis-related protein, heat-shock protein, thaumatin/osmotin-like proteins, cytochrome P450, lipid-transfer proteins, and calcium-binding proteins. A selected-gene interaction contrast prioritized LITCHI019519, LITCHI001510, LITCHI028401, LITCHI017676, LITCHI028104, and LITCHI019183 as potential cultivar-dependent response genes. Promoter analysis of 2-kb upstream regions detected stress- and hormone-associated cis-elements, and a random-promoter background test supported enrichment of ARE, MeJA-responsive motifs, TCA-elements, and TC-rich repeats. These results provide testable candidates for future functional validation of lychee resistance to P. litchii.