RNAseq biological replicates not clustering in PCA plots

You used Kallisto for alignment. I think Kallisto reports TPM values, are you using this value? DEseq2 uses count data, so I am not sure whether these two methods are compatible.

Also, I agree with previous answers that your PCA actually looks OK. One possible way to improve is to choose top variable genes. For example, you can try top 3,000, 5,000, 7,000 genes and so on. The idea is that for the genes that do not show much variation between samples, including them in PCA may just introduce noise. You can also try to color samples in your PCA by some other variables, like batch, sequencing depth and so on to trouble-shooting.

Clustering of replicates looks decent enough to me, so you should be abl to push ahead, but I agree the tissues are grouping, which could mask any differences based on sex or genotype.

You might consider the EdgeR package for DE analysis here. It allows for flexibility when making complex comparisons while accounting for tissue/batch effects. I've had good luck with using it to compare across batch effects from complex experiments like this.

PC1 is 81% of the variance?

This PCA plot confirms that different tissues are different. You probably already knew that. I'd make more PCA plots that are tissue specific. That will be more informative than these.

Personally, I'd also not do DESeq on all of these samples together, unless the goal of your experiment really is to learn the differences between these two tissues.